Pub Date : 2024-06-11DOI: 10.1016/j.molimm.2024.06.003
QiHong Wu , Mengyue Wu , Kun Zhang , Ran Sun , Hong Li , Jiyu Tong , Yingkun Guo
Acute myocardial infarction (AMI), mainly triggered by vascular occlusion or thrombosis, is the most prevalent cause of morbidity and mortality among all cardiovascular diseases. The devastating consequences of AMI are further aggravated by the intricate cellular processes involved in inflammation. In the past two decades, many studies have reported that regulatory T cells (Tregs), as the main immunoregulatory cells, play a crucial role in AMI progression. This review offers a comprehensive insight into the intricate relationship between Tregs and AMI development. Moreover, it explores emerging therapeutic strategies that focus on Tregs and their exosomes. Furthermore, we underscore the importance of employing noninvasive in vivo imaging techniques to advance the clinical applications of Tregs-based treatments in AMI. Although further research is essential to fully elucidate the molecular mechanisms underlying the effects of Tregs, therapies tailored to these cells hold immense potential for the treatment of patients with AMI.
急性心肌梗死(AMI)主要由血管闭塞或血栓形成引发,是所有心血管疾病中发病率和死亡率最高的原因。炎症所涉及的复杂细胞过程进一步加剧了急性心肌梗死的破坏性后果。在过去二十年中,许多研究报告称,调节性 T 细胞(Tregs)作为主要的免疫调节细胞,在急性心肌梗死的进展过程中发挥着至关重要的作用。本综述全面探讨了调节性 T 细胞与 AMI 发展之间错综复杂的关系。此外,它还探讨了以Tregs及其外泌体为重点的新兴治疗策略。此外,我们还强调了采用非侵入性体内成像技术推动基于 Tregs 的 AMI 治疗临床应用的重要性。尽管进一步的研究对全面阐明Tregs作用的分子机制至关重要,但针对这些细胞的疗法在治疗AMI患者方面潜力巨大。
{"title":"Regulatory T cells as a therapeutic target in acute myocardial infarction","authors":"QiHong Wu , Mengyue Wu , Kun Zhang , Ran Sun , Hong Li , Jiyu Tong , Yingkun Guo","doi":"10.1016/j.molimm.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.06.003","url":null,"abstract":"<div><p>Acute myocardial infarction (AMI), mainly triggered by vascular occlusion or thrombosis, is the most prevalent cause of morbidity and mortality among all cardiovascular diseases. The devastating consequences of AMI are further aggravated by the intricate cellular processes involved in inflammation. In the past two decades, many studies have reported that regulatory T cells (Tregs), as the main immunoregulatory cells, play a crucial role in AMI progression. This review offers a comprehensive insight into the intricate relationship between Tregs and AMI development. Moreover, it explores emerging therapeutic strategies that focus on Tregs and their exosomes. Furthermore, we underscore the importance of employing noninvasive <em>in vivo</em> imaging techniques to advance the clinical applications of Tregs-based treatments in AMI. Although further research is essential to fully elucidate the molecular mechanisms underlying the effects of Tregs, therapies tailored to these cells hold immense potential for the treatment of patients with AMI.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-11DOI: 10.1016/j.molimm.2024.05.011
Hua Yang , Cai Zhou , Shenglan Nie , Shuling Xu , Mengqing Li , Qinyao Yu , Yunpeng Wei , Xiaomei Wang
Ulcerative colitis (UC) is a prevalent inflammatory disorder that emerges in the colon and rectum, exhibiting a rising global prevalence and seriously impacting the physical and mental health of patients. Significant challenges remain in UC treatment, highlighting the need for safe and effective long-term therapeutic approaches. Heralded as a promising physical treatment, the rotating magnetic field (RMF) demonstrates safety, stability, manageability, and efficiency. This study delves into RMF’s potential in mitigating DSS-induced UC in mice, assessing disease activity indices (DAI) and pathological alterations such as daily body weight, fecal occult blood, colon length, and morphological changes. Besides, several indexes have been detected, including serum concentrations of pro-inflammatory cytokines (IL6, IL-17A, TNF-α, IFN-γ) and anti-inflammatory cytokines (TGF-β, IL-4, IL-10), the ratio of splenic CD3+, CD4+, and CD8+ T cells, the rate of apoptotic colonic cells, the expression of colonic inflammatory and tight junction-associated proteins. The results showed that RMF had beneficial effects on the decrease of intestinal permeability, the restoration of tight junctions, and the mitigation of mitochondrial respiratory complexes (MRCs) by attenuating inflammatory dysfunction in colons of DSS-induced UC model of mice. In conclusion, this study demonstrates that RMF attenuates colonic inflammation, enhances colonic tight junction, and alleviates MRCs impairment by regulating the equilibrium of pro-inflammatory and anti-inflammatory cytokines in UC mice, suggesting the potential application of RMF in the clinical treatment of UC.
{"title":"Anti-ulcerative colitis effect of rotating magnetic field on DSS-induced mice by modulating colonic inflammatory deterioration","authors":"Hua Yang , Cai Zhou , Shenglan Nie , Shuling Xu , Mengqing Li , Qinyao Yu , Yunpeng Wei , Xiaomei Wang","doi":"10.1016/j.molimm.2024.05.011","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.011","url":null,"abstract":"<div><p>Ulcerative colitis (UC) is a prevalent inflammatory disorder that emerges in the colon and rectum, exhibiting a rising global prevalence and seriously impacting the physical and mental health of patients. Significant challenges remain in UC treatment, highlighting the need for safe and effective long-term therapeutic approaches. Heralded as a promising physical treatment, the rotating magnetic field (RMF) demonstrates safety, stability, manageability, and efficiency. This study delves into RMF’s potential in mitigating DSS-induced UC in mice, assessing disease activity indices (DAI) and pathological alterations such as daily body weight, fecal occult blood, colon length, and morphological changes. Besides, several indexes have been detected, including serum concentrations of pro-inflammatory cytokines (IL6, IL-17A, TNF-α, IFN-γ) and anti-inflammatory cytokines (TGF-β, IL-4, IL-10), the ratio of splenic CD3+, CD4+, and CD8+ T cells, the rate of apoptotic colonic cells, the expression of colonic inflammatory and tight junction-associated proteins. The results showed that RMF had beneficial effects on the decrease of intestinal permeability, the restoration of tight junctions, and the mitigation of mitochondrial respiratory complexes (MRCs) by attenuating inflammatory dysfunction in colons of DSS-induced UC model of mice. In conclusion, this study demonstrates that RMF attenuates colonic inflammation, enhances colonic tight junction, and alleviates MRCs impairment by regulating the equilibrium of pro-inflammatory and anti-inflammatory cytokines in UC mice, suggesting the potential application of RMF in the clinical treatment of UC.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161589024001020/pdfft?md5=b2d41aac1f221b1c952260625780b69c&pid=1-s2.0-S0161589024001020-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HIV/HCV coinfection is associated with a rapid progression to liver damage. Specifically, NK cell population dysregulation is of particular interest, as these cells have been shown to block HCV replication effectively and have an anti-fibrogenic activity. The NKp30 receptor is linked to tumor cell lysis and has a crucial role during viral infections. In the present study, we determined the subpopulations of NK cells based on CD56 and CD16 expression, NKp30 receptor expression, its isoforms A, B, and C, along with the cytotoxicity molecules in patients with HIV/HCV. Results: evidenced by the APRI and FIB-4 indices, the HCV-infected patients presented greater liver damage than the HIV and HIV/HCV groups. The HCV group presented a decreased expression of NKp30 isoform A, and NK cell frequency was not different between groups; however, CD56brigth subpopulation, NKp30 receptor, and CD247 adaptor chain were decreased in HIV/HCV patients; further, we described increased levels of soluble IL-8, IL-10, IL-12, and IL-23 in the serum of HIV/HCV patients. Conclusions: HCV and HIV/HCV patients have multiple parameters of non-fitness status in NK cells; awareness of these dysfunctional immunological parameters in HIV/HCV and HCV patients can elucidate possible novel therapeutics directed towards the improvement of NK cell fitness status, in order to improve their function against liver damage.
背景艾滋病毒/丙型肝炎病毒(HIV/HCV)合并感染与肝损伤的快速进展有关。NK 细胞群失调尤其令人关注,因为这些细胞已被证明能有效阻断 HCV 复制并具有抗纤维化活性。NKp30 受体与肿瘤细胞裂解有关,在病毒感染过程中起着至关重要的作用。在本研究中,我们根据 HIV/HCV 患者的 CD56 和 CD16 表达、NKp30 受体表达、其同工酶 A、B 和 C 以及细胞毒性分子确定了 NK 细胞亚群。结果:从 APRI 和 FIB-4 指数来看,HCV 感染者的肝损伤程度高于 HIV 组和 HIV/HCV 组。HCV组的NKp30同工酶A表达减少,NK细胞频率在组间无差异;但HIV/HCV患者的CD56brigth亚群、NKp30受体和CD247适配链减少;此外,我们发现HIV/HCV患者血清中可溶性IL-8、IL-10、IL-12和IL-23水平升高。结论HCV和HIV/HCV患者的NK细胞有多个参数处于非适配状态;了解HIV/HCV和HCV患者的这些功能失调的免疫学参数,可以阐明改善NK细胞适配状态的新型疗法,从而提高它们对抗肝损伤的功能。
{"title":"Unraveling the non-fitness status of NK cells: Examining the NKp30 receptor and its isoforms distribution in HIV/HCV coinfected patients","authors":"Cecilia Gutiérrez-Iñiguez , Paulina Cervantes-Rodríguez , Luz Alicia González-Hernández , Jaime Federico Andrade-Villanueva , Gloria Yareli Gutiérrez-Silerio , Marcela Peña Rodríguez , Alina Xcaret Rubio-Sánchez , Estefania García-Castillo , María Eugenia Marín-Contreras , Susana Del Toro-Arreola , Miriam Ruth Bueno-Topete , Natali Vega-Magaña","doi":"10.1016/j.molimm.2024.05.010","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.010","url":null,"abstract":"<div><h3>Background</h3><p>HIV/HCV coinfection is associated with a rapid progression to liver damage. Specifically, NK cell population dysregulation is of particular interest, as these cells have been shown to block HCV replication effectively and have an anti-fibrogenic activity. The NKp30 receptor is linked to tumor cell lysis and has a crucial role during viral infections. In the present study, we determined the subpopulations of NK cells based on CD56 and CD16 expression, NKp30 receptor expression, its isoforms A, B, and C, along with the cytotoxicity molecules in patients with HIV/HCV. Results: evidenced by the APRI and FIB-4 indices, the HCV-infected patients presented greater liver damage than the HIV and HIV/HCV groups. The HCV group presented a decreased expression of NKp30 isoform A, and NK cell frequency was not different between groups; however, CD56<sup>brigth</sup> subpopulation, NKp30 receptor, and CD247 adaptor chain were decreased in HIV/HCV patients; further, we described increased levels of soluble IL-8, IL-10, IL-12, and IL-23 in the serum of HIV/HCV patients. Conclusions: HCV and HIV/HCV patients have multiple parameters of non-fitness status in NK cells; awareness of these dysfunctional immunological parameters in HIV/HCV and HCV patients can elucidate possible novel therapeutics directed towards the improvement of NK cell fitness status, in order to improve their function against liver damage.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161589024001019/pdfft?md5=f49bb6735a04e45690b13105f7c373d1&pid=1-s2.0-S0161589024001019-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-07DOI: 10.1016/j.molimm.2024.05.009
Haixia Wang , Yadan Nie , Zuoli Sun , Yi He , Jian Yang
Serum amyloid P component (SAP) is a member the innate immune humoral arm and participated in various processes, including the innate immune responses, tissue remodeling, and the pathogenesis of inflammatory diseases. Remarkably, SAP is a highly versatile immunomodulatory factor that can serve as a drug target for treating amyloid diseases and reduce inflammation, fibrosis degree, and respiratory disease. In this review, we focus on the biological activities of SAP and its application in different systemic immune-associated diseases. First, we reviewed the regulatory effects of SAP on innate immune cells and possible mechanisms. Second, we emphasized SAP as a diagnostic marker and therapeutic target for immune-associated diseases, including the neuropsychiatric disorders. Third, we presented several recommendations for regulating SAP in immune cell function and potential areas for future research. Some authorities consider SAP to be a pattern recognition molecule that plays multiple roles in the innate immune system and inflammation. Developing therapeutics that target SAP or its associated signaling pathways may be a promising strategy for treating immune-associated diseases.
血清淀粉样蛋白 P 成分(SAP)是先天性免疫体液臂的成员之一,参与先天性免疫反应、组织重塑和炎症性疾病发病机制等多个过程。值得注意的是,SAP 是一种用途广泛的免疫调节因子,可作为治疗淀粉样蛋白疾病的药物靶点,并能减轻炎症、纤维化程度和呼吸系统疾病。在这篇综述中,我们重点探讨了 SAP 的生物活性及其在不同系统性免疫相关疾病中的应用。首先,我们回顾了 SAP 对先天性免疫细胞的调节作用及其可能的机制。其次,我们强调了 SAP 作为免疫相关疾病(包括神经精神疾病)的诊断标志物和治疗靶点的作用。第三,我们就如何调节 SAP 在免疫细胞功能中的作用以及未来研究的潜在领域提出了一些建议。一些权威人士认为,SAP 是一种模式识别分子,在先天性免疫系统和炎症中发挥着多重作用。开发针对SAP或其相关信号通路的疗法可能是治疗免疫相关疾病的一种有前途的策略。
{"title":"Serum amyloid P component: Structure, biological activity, and application in diagnosis and treatment of immune-associated diseases","authors":"Haixia Wang , Yadan Nie , Zuoli Sun , Yi He , Jian Yang","doi":"10.1016/j.molimm.2024.05.009","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.009","url":null,"abstract":"<div><p>Serum amyloid P component (SAP) is a member the innate immune humoral arm and participated in various processes, including the innate immune responses, tissue remodeling, and the pathogenesis of inflammatory diseases. Remarkably, SAP is a highly versatile immunomodulatory factor that can serve as a drug target for treating amyloid diseases and reduce inflammation, fibrosis degree, and respiratory disease. In this review, we focus on the biological activities of SAP and its application in different systemic immune-associated diseases. First, we reviewed the regulatory effects of SAP on innate immune cells and possible mechanisms. Second, we emphasized SAP as a diagnostic marker and therapeutic target for immune-associated diseases, including the neuropsychiatric disorders. Third, we presented several recommendations for regulating SAP in immune cell function and potential areas for future research. Some authorities consider SAP to be a pattern recognition molecule that plays multiple roles in the innate immune system and inflammation. Developing therapeutics that target SAP or its associated signaling pathways may be a promising strategy for treating immune-associated diseases.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161589024001007/pdfft?md5=8ca44b9fd52dfebe0d3d3b79035f26f8&pid=1-s2.0-S0161589024001007-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05DOI: 10.1016/j.molimm.2024.04.014
Xinyi Zhang , Yun Zou , Yuqi Liu , Yumeng Cao , Jiali Zhu , Jianhai Zhang , Xia Chen , Rui Zhang , Jinbao Li
{"title":"Corrigendum to “Inhibition of PIM1 kinase attenuates bleomycin-induced pulmonary fibrosis in mice by modulating the ZEB1/E-cadherin pathway in alveolar epithelial cells” [Mol. Immunol. 125 (2020) 15–22]","authors":"Xinyi Zhang , Yun Zou , Yuqi Liu , Yumeng Cao , Jiali Zhu , Jianhai Zhang , Xia Chen , Rui Zhang , Jinbao Li","doi":"10.1016/j.molimm.2024.04.014","DOIUrl":"10.1016/j.molimm.2024.04.014","url":null,"abstract":"","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161589024000841/pdfft?md5=ade6c7d72f681e6a9e39d406321da602&pid=1-s2.0-S0161589024000841-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-30DOI: 10.1016/j.molimm.2024.05.007
Zhou Si Yun , Song Zhihua , Tian Xuelian , Xia Min , Hu Rongjing , Luo Mei
Chlamydia trachomatis (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice.
沙眼衣原体(CT)是全球细菌性性传播疾病的主要病原体,可引起盆腔炎、宫颈和输卵管炎等疾病,对人类健康构成威胁。迷迭香酸(RosA)是天然产品的一种活性成分,具有抗炎和免疫调节作用。本研究旨在探讨 RosA 在 CT 感染小鼠模型中通过 Ras/Raf/MEK/ERK 信号通路抑制自噬调节的免疫细胞-CD8+ T 细胞的作用。小鼠经阴道接种CT感染液,采用H&E染色、流式细胞术、免疫荧光、透射电子显微镜和Western blot等方法确定了RosA治疗的机理基础。使用 MEK 抑制剂 cobimetinib 进一步验证了参与 RosA 治疗的关键因素。实验结果表明,RosA和参比药物阿奇霉素都能减轻CT感染对子宫内膜造成的病理损伤;流式细胞术显示,CT感染后外周血CD8+T细胞增加,而RosA和阳性药物阿奇霉素(阳性对照)治疗后CD8+T细胞减少;免疫荧光显示,CT感染后子宫内膜CD8和LC3增加,RosA和阳性药物治疗后减少;透射电镜结果显示,RosA和阳性药物阿奇霉素抑制了自噬体的积累;Western bolt实验证实,CT感染后自噬蛋白LC3Ⅱ/Ⅰ、ATG5、Beclin-1和p62被激活,Ras/Raf/MEK/ERK信号转导受到抑制。RosA和阿奇霉素抑制自噬蛋白可激活Ras/Raf/MEK/ERK信号。此外,MEK抑制剂cobimetinib在CT诱导的基础上进一步激活CD8+ T细胞,从而削弱了RosA对子宫内膜的保护作用,而透射电镜、免疫荧光和Western印迹显示,cobimetinib阻断了ERK信号的激活,并在CT诱导的基础上进一步诱导了吞噬作用。这些数据表明,RosA能激活Ras/Raf/MEK/ERK信号通路以抑制自噬,RosA还能调节免疫细胞-CD8+T细胞的活化,从而保护CT感染小鼠的生殖道。
{"title":"Rosmarinic acid activates the Ras/Raf/MEK/ERK signaling pathway to regulate CD8+ T cells and autophagy to clear Chlamydia trachomatis in reproductive tract-infected mice","authors":"Zhou Si Yun , Song Zhihua , Tian Xuelian , Xia Min , Hu Rongjing , Luo Mei","doi":"10.1016/j.molimm.2024.05.007","DOIUrl":"10.1016/j.molimm.2024.05.007","url":null,"abstract":"<div><p><em>Chlamydia trachomatis</em> (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-27DOI: 10.1016/j.molimm.2024.05.008
Wen Wang , Kangle Zhang , Lingling Dai , Aihua Hou , Peng Meng , Jipeng Ma
Background
This study determines the role and mechanism of APS in cyclophosphamide-induced myelosuppression in mice and bone mesenchymal stem cells (BMSCs) cell model.
Methods
Cy-induced myelosuppression mice and BMSCs cell model were established. Fifty C57BL/6 mice (weighing 20 ± 2 g) were randomly divided into five groups. Femur and tibia samples, bone marrow samples, and blood samples were collected 3 days after the last injection of Cy. Histopathology changes and cell apoptosis were detected. Cell viability, apoptosis, cycle distribution, reactive oxygen species activity, osteogenesis ability, and protein levels were detected. γ-H2AX and senescence-associated β-galactosidase activity expression was detected by immunofluorescence. Cy-induced senescence and Wnt/β-catenin related protein levels were detected using western blotting.
Results
The results showed that APS effectively induced Cy-induced histological injury and cell apoptosis rate. After treated with APS, ROS and ALP levels were significantly increased. In BMSCs, cell viability, apoptosis, and cell cycle distribution were also influenced by APS treatment. Compared with the control group, cell viability was significantly increased, the cell apoptosis rate was decreased while the number of cells remained in the G0-G1 phase was increased. Meanwhile, ROS levels were significantly increased in APS group. Cell senescence and Wnt/β-catenin related protein (γ-H2AX, SA-β-gal, p21, p16, p-β-catenin/ β-catenin, c-Myc, and AXIN2) levels were also altered both in vivo and in vitro. Interestingly, the effects of APS were reversed by BML-284.
Conclusion
Our results indicate that APS protected Cy-induced myelosuppression through the Wnt/β-catenin pathway and APS is a potential therapeutic drug for Cy-induced myelosuppression.
{"title":"Investigating the protective effects of Astragalus polysaccharides on cyclophosphamide-induced bone marrow suppression in mice and bone mesenchymal stem cells","authors":"Wen Wang , Kangle Zhang , Lingling Dai , Aihua Hou , Peng Meng , Jipeng Ma","doi":"10.1016/j.molimm.2024.05.008","DOIUrl":"10.1016/j.molimm.2024.05.008","url":null,"abstract":"<div><h3>Background</h3><p>This study determines the role and mechanism of APS in cyclophosphamide-induced myelosuppression in mice and bone mesenchymal stem cells (BMSCs) cell model.</p></div><div><h3>Methods</h3><p>Cy-induced myelosuppression mice and BMSCs cell model were established. Fifty C57BL/6 mice (weighing 20 ± 2 g) were randomly divided into five groups. Femur and tibia samples, bone marrow samples, and blood samples were collected 3 days after the last injection of Cy. Histopathology changes and cell apoptosis were detected. Cell viability, apoptosis, cycle distribution, reactive oxygen species activity, osteogenesis ability, and protein levels were detected. γ-H2AX and senescence-associated β-galactosidase activity expression was detected by immunofluorescence. Cy-induced senescence and Wnt/β-catenin related protein levels were detected using western blotting.</p></div><div><h3>Results</h3><p>The results showed that APS effectively induced Cy-induced histological injury and cell apoptosis rate. After treated with APS, ROS and ALP levels were significantly increased. In BMSCs, cell viability, apoptosis, and cell cycle distribution were also influenced by APS treatment. Compared with the control group, cell viability was significantly increased, the cell apoptosis rate was decreased while the number of cells remained in the G0-G1 phase was increased. Meanwhile, ROS levels were significantly increased in APS group. Cell senescence and Wnt/β-catenin related protein (γ-H2AX, SA-β-gal, p21, p16, p-β-catenin/ β-catenin, c-Myc, and AXIN2) levels were also altered both <em>in vivo</em> and <em>in vitro</em>. Interestingly, the effects of APS were reversed by BML-284.</p></div><div><h3>Conclusion</h3><p>Our results indicate that APS protected Cy-induced myelosuppression through the Wnt/β-catenin pathway and APS is a potential therapeutic drug for Cy-induced myelosuppression.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.1016/j.molimm.2024.05.006
Xiaowen Li , Wenling Wang , Jie Wang , Min Jiang , Juanhua He , Shuguang Tan
The oncogenic protein E7 of the Human Papillomavirus (HPV) is constitutionally expressed in HPV-associated tumors and has the potential to be targeted in T cell receptor (TCR)-based immunotherapy. Adoptive transfer of TCR-engineered T (TCR-T) cells has shown promise as a therapeutic approach for HPV-induced tumors. This study aimed to identify HPV-E7 specific TCRs from HLA-A11:01 transgenic mice through single-cell sorting and sequencing facilitated by E789–97/HLA-A11:01 tetramer. Two dominant TCRs were identified, which exhibited specific binding to E789–97 presented in the context of HLA-A*11:01. TCR-T cells were prepared by infecting primary T cells with lentiviruses containing the TCR genes, and the two TCRs demonstrated substantial responsiveness and showed CD8+ dependent cytokine secretion characteristics. Further analyses of the cytokine profiles revealed that the two TCRs were capable of exerting polyfunctional responses upon specific stimulation. These findings suggest that the two TCRs represent promising candidates for the development of future therapeutic drugs targeting HPV-E7 in the context of HLA-A*11:01 for tumor immunotherapy.
{"title":"Identification of HPV-E7 specific TCRs for tumor immunotherapy","authors":"Xiaowen Li , Wenling Wang , Jie Wang , Min Jiang , Juanhua He , Shuguang Tan","doi":"10.1016/j.molimm.2024.05.006","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.006","url":null,"abstract":"<div><p>The oncogenic protein E7 of the Human Papillomavirus (HPV) is constitutionally expressed in HPV-associated tumors and has the potential to be targeted in T cell receptor (TCR)-based immunotherapy. Adoptive transfer of TCR-engineered T (TCR-T) cells has shown promise as a therapeutic approach for HPV-induced tumors. This study aimed to identify HPV-E7 specific TCRs from HLA-A11:01 transgenic mice through single-cell sorting and sequencing facilitated by E7<sub>89–97</sub>/HLA-A11:01 tetramer. Two dominant TCRs were identified, which exhibited specific binding to E7<sub>89–97</sub> presented in the context of HLA-A*11:01. TCR-T cells were prepared by infecting primary T cells with lentiviruses containing the TCR genes, and the two TCRs demonstrated substantial responsiveness and showed CD8+ dependent cytokine secretion characteristics. Further analyses of the cytokine profiles revealed that the two TCRs were capable of exerting polyfunctional responses upon specific stimulation. These findings suggest that the two TCRs represent promising candidates for the development of future therapeutic drugs targeting HPV-E7 in the context of HLA-A*11:01 for tumor immunotherapy.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.1016/j.molimm.2024.05.005
Yung-Lan Chou , Yu-An Hsu , Chi-Fong Lin , Chih-Sheng Chen , Peng-Tai Tien , Yao-Chien Wang , Ching-Yao Chang , En-Shyh Lin , Jamie Jiin-Yi Chen , Ming-Yen Wu , Chun-Yu Chuang , Hui-Ju Lin , Lei Wan
Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-β, IL-6, TNF-α, and IL-1β may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-β) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.
{"title":"Complement decay-accelerating factor inhibits inflammation-induced myopia development","authors":"Yung-Lan Chou , Yu-An Hsu , Chi-Fong Lin , Chih-Sheng Chen , Peng-Tai Tien , Yao-Chien Wang , Ching-Yao Chang , En-Shyh Lin , Jamie Jiin-Yi Chen , Ming-Yen Wu , Chun-Yu Chuang , Hui-Ju Lin , Lei Wan","doi":"10.1016/j.molimm.2024.05.005","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.005","url":null,"abstract":"<div><p>Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-β, IL-6, TNF-α, and IL-1β may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-β) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.1016/j.molimm.2024.05.004
Sofía Quesada , Ayelén Daiana Rosso , Florencia Mascardi , Valeria Soler-Rivero , Pablo Aguilera , Sebastian Nicolas Mascuka , Andrea Boiro , Evangelina Arenielo , Gustavo Vijoditz , Leila Romina Ferreyra-Mufarregue , Marina Flavia Caputo , María Cecilia Cimolai , Federico Coluccio Leskow , Alberto Penas-Steinhardt , Fiorella Sabrina Belforte
Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223–3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223–3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.
{"title":"Integrative analysis of systemic lupus erythematosus biomarkers: Role of fecal hsa-mir-223–3p and gut microbiota in transkingdom dynamics","authors":"Sofía Quesada , Ayelén Daiana Rosso , Florencia Mascardi , Valeria Soler-Rivero , Pablo Aguilera , Sebastian Nicolas Mascuka , Andrea Boiro , Evangelina Arenielo , Gustavo Vijoditz , Leila Romina Ferreyra-Mufarregue , Marina Flavia Caputo , María Cecilia Cimolai , Federico Coluccio Leskow , Alberto Penas-Steinhardt , Fiorella Sabrina Belforte","doi":"10.1016/j.molimm.2024.05.004","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.004","url":null,"abstract":"<div><p>Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223–3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, <em>Collinsella, Bifidobacterium, Streptococcus</em> genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223–3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}