Pub Date : 2024-04-01Epub Date: 2024-02-02DOI: 10.1111/sji.13361
Daijiao Ye, Jiayao He, Xiaofei He
Takeda G protein-coupled receptor 5 (TGR5) is a bile acid receptor, and its role in regulating metabolism after binding with bile acids has been established. Since the immune response depends on metabolism to provide biomolecules and energy to cope with challenging conditions, emerging evidence reveals the regulatory effects of TGR5 on the immune response. An in-depth understanding of the effect of TGR5 on immune regulation can help us disentangle the interaction of metabolism and immune response, accelerating the development of TGR5 as a therapeutic target. Herein, we reviewed more than 200 articles published in the last 20 years in PubMed, to discuss the roles of TGR5 in regulating inflammatory response, the molecular mechanism, as well as existing problems. Particularly, its anti-inflammation effect is emphasized.
武田 G 蛋白偶联受体 5（TGR5）是一种胆汁酸受体，它与胆汁酸结合后在调节新陈代谢方面的作用已被证实。由于免疫反应依赖于新陈代谢来提供生物分子和能量以应对具有挑战性的条件，新的证据揭示了 TGR5 对免疫反应的调节作用。深入了解 TGR5 对免疫调节的影响有助于我们厘清新陈代谢与免疫反应之间的相互作用，从而加速 TGR5 作为治疗靶点的开发。在此，我们回顾了近20年发表在PubMed上的200多篇文章，探讨了TGR5在调节炎症反应中的作用、分子机制以及存在的问题。特别强调了其抗炎作用。
{"title":"The role of bile acid receptor TGR5 in regulating inflammatory signalling.","authors":"Daijiao Ye, Jiayao He, Xiaofei He","doi":"10.1111/sji.13361","DOIUrl":"10.1111/sji.13361","url":null,"abstract":"<p><p>Takeda G protein-coupled receptor 5 (TGR5) is a bile acid receptor, and its role in regulating metabolism after binding with bile acids has been established. Since the immune response depends on metabolism to provide biomolecules and energy to cope with challenging conditions, emerging evidence reveals the regulatory effects of TGR5 on the immune response. An in-depth understanding of the effect of TGR5 on immune regulation can help us disentangle the interaction of metabolism and immune response, accelerating the development of TGR5 as a therapeutic target. Herein, we reviewed more than 200 articles published in the last 20 years in PubMed, to discuss the roles of TGR5 in regulating inflammatory response, the molecular mechanism, as well as existing problems. Particularly, its anti-inflammation effect is emphasized.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Barbora Bacova, Jakub Cierny, Lucia Nemcekova, Jitka Smetanova/Brozova, Jan Novak
Mucosal‐associated invariant T‐cells (MAIT) are unconventional T‐cells with cytotoxic and pro‐inflammatory properties. Previous research has reported contradictory findings on their role in cancerogenesis with data being even scarcer in haematological malignancies. Here, we report the results of a systematic analysis of MAIT cells in treatment‐naïve patients with a broad range of haematological malignancies. We analysed peripheral blood of 204 patients and 50 healthy subjects. The pool of haematological patients had a statistically significant lower both the absolute value (median values, 0.01 × 109/L vs. 0.05 × 109/L) of MAIT cells and their percentage (median values 0.94% vs. 2.56%) among T‐cells compared to the control group. Separate analysis showed that the decrease in the absolute number of MAIT cells is significant in patients with acute myeloid leukaemia, myeloproliferative neoplasms, plasma cell myeloma, B‐cell non‐Hodgkin lymphomas, otherwise not specified, diffuse large B‐cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma compared to the control population. Furthermore, in haematological malignancies, MAIT cells overexpress PD‐1 (average values, 51.7% vs. 6.7%), HLA‐DR (average values, 40.2% vs. 7%), CD38 (average values, 25.9% vs. 4.9%) and CD69 (average values, 40.2% vs. 9.2%). Similar results were obtained when comparing patients with individual malignancies to the control population. Our data show that the depletion of circulating MAIT cells is a common observation in a broad spectrum of haematological malignancies. In addition to their reduced numbers, MAIT cells acquire an activated/exhausted phenotype.
{"title":"Systematic analysis of mucosal‐associated invariant T cells in haematological malignancies","authors":"Barbora Bacova, Jakub Cierny, Lucia Nemcekova, Jitka Smetanova/Brozova, Jan Novak","doi":"10.1111/sji.13364","DOIUrl":"https://doi.org/10.1111/sji.13364","url":null,"abstract":"Mucosal‐associated invariant T‐cells (MAIT) are unconventional T‐cells with cytotoxic and pro‐inflammatory properties. Previous research has reported contradictory findings on their role in cancerogenesis with data being even scarcer in haematological malignancies. Here, we report the results of a systematic analysis of MAIT cells in treatment‐naïve patients with a broad range of haematological malignancies. We analysed peripheral blood of 204 patients and 50 healthy subjects. The pool of haematological patients had a statistically significant lower both the absolute value (median values, 0.01 × 10<jats:sup>9</jats:sup>/L vs. 0.05 × 10<jats:sup>9</jats:sup>/L) of MAIT cells and their percentage (median values 0.94% vs. 2.56%) among T‐cells compared to the control group. Separate analysis showed that the decrease in the absolute number of MAIT cells is significant in patients with acute myeloid leukaemia, myeloproliferative neoplasms, plasma cell myeloma, B‐cell non‐Hodgkin lymphomas, otherwise not specified, diffuse large B‐cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma compared to the control population. Furthermore, in haematological malignancies, MAIT cells overexpress PD‐1 (average values, 51.7% vs. 6.7%), HLA‐DR (average values, 40.2% vs. 7%), CD38 (average values, 25.9% vs. 4.9%) and CD69 (average values, 40.2% vs. 9.2%). Similar results were obtained when comparing patients with individual malignancies to the control population. Our data show that the depletion of circulating MAIT cells is a common observation in a broad spectrum of haematological malignancies. In addition to their reduced numbers, MAIT cells acquire an activated/exhausted phenotype.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140053698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antiphospholipid syndrome is a rare autoimmune disease characterized by persistent antiphospholipid antibodies. Immunoglobulin G plays a vital role in disease progression, with its structure and function affected by glycosylation. We aimed to investigate the changes in the serum immunoglobulin G glycosylation pattern in antiphospholipid syndrome patients. We applied lectin microarray on samples from 178 antiphospholipid syndrome patients, 135 disease controls (including Takayasu arteritis, rheumatoid arthritis and cardiovascular disease) and 100 healthy controls. Lectin blots were performed for validation of significant differences. Here, we show an increased immunoglobulin G‐binding level of soybean agglutinin (p = 0.047, preferring N‐acetylgalactosamine) in antiphospholipid syndrome patients compared with healthy and disease controls. Additionally, the immunoglobulin G from antiphospholipid syndrome patients diagnosed with pregnancy events had lower levels of fucosylation (p = 0.001, recognized by Lotus tetragonolobus) and sialylation (p = 0.030, recognized by Sambucus nigra I) than those with simple thrombotic events. These results suggest the unique serum immunoglobulin G glycosylation profile of antiphospholipid syndrome patients, which may inform future studies to design biomarkers for more accurate diagnosis of antiphospholipid syndrome and even for the prediction of clinical symptoms in patients.
抗磷脂综合征是一种罕见的自身免疫性疾病，其特征是持续存在抗磷脂抗体。免疫球蛋白G在疾病进展中起着至关重要的作用，其结构和功能受糖基化的影响。我们旨在研究抗磷脂综合征患者血清免疫球蛋白G糖基化模式的变化。我们对 178 名抗磷脂综合征患者、135 名疾病对照组（包括高安动脉炎、类风湿性关节炎和心血管疾病）和 100 名健康对照组的样本进行了凝集素芯片分析。为验证显著差异，还进行了凝集素印迹分析。在此，我们发现与健康对照组和疾病对照组相比，抗磷脂综合征患者体内大豆凝集素的免疫球蛋白 G 结合水平升高（p = 0.047，更倾向于 N-乙酰半乳糖胺）。此外，与单纯血栓事件患者相比，被诊断为妊娠事件的抗磷脂综合征患者的免疫球蛋白 G 的岩藻糖基化（p = 0.001，被四角莲识别）和硅烷基化（p = 0.030，被黑三叶草 I 识别）水平较低。这些结果表明，抗磷脂综合征患者的血清免疫球蛋白G糖基化谱具有独特性，可为今后的研究提供参考，从而设计出生物标记物，更准确地诊断抗磷脂综合征，甚至预测患者的临床症状。
{"title":"Changes in serum immunoglobulin G glycosylation patterns for antiphospholipid syndrome patients with lectin microarray","authors":"Yifei Wang, Siting Li, Jingjing Meng, Rui Yu, Qian Wang, Xinping Tian, Mengtao Li, Xiaofeng Zeng, Jiulang Zhao, Chaojun Hu","doi":"10.1111/sji.13366","DOIUrl":"https://doi.org/10.1111/sji.13366","url":null,"abstract":"Antiphospholipid syndrome is a rare autoimmune disease characterized by persistent antiphospholipid antibodies. Immunoglobulin G plays a vital role in disease progression, with its structure and function affected by glycosylation. We aimed to investigate the changes in the serum immunoglobulin G glycosylation pattern in antiphospholipid syndrome patients. We applied lectin microarray on samples from 178 antiphospholipid syndrome patients, 135 disease controls (including Takayasu arteritis, rheumatoid arthritis and cardiovascular disease) and 100 healthy controls. Lectin blots were performed for validation of significant differences. Here, we show an increased immunoglobulin G‐binding level of soybean agglutinin (<jats:italic>p</jats:italic> = 0.047, preferring N‐acetylgalactosamine) in antiphospholipid syndrome patients compared with healthy and disease controls. Additionally, the immunoglobulin G from antiphospholipid syndrome patients diagnosed with pregnancy events had lower levels of fucosylation (<jats:italic>p</jats:italic> = 0.001, recognized by <jats:italic>Lotus tetragonolobus</jats:italic>) and sialylation (<jats:italic>p</jats:italic> = 0.030, recognized by <jats:italic>Sambucus nigra</jats:italic> I) than those with simple thrombotic events. These results suggest the unique serum immunoglobulin G glycosylation profile of antiphospholipid syndrome patients, which may inform future studies to design biomarkers for more accurate diagnosis of antiphospholipid syndrome and even for the prediction of clinical symptoms in patients.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140046310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood‐borne pathogen (BBP) infections can rapidly progress to life‐threatening sepsis and must therefore be promptly eliminated by the host's immune system. Intravascular macrophages of the liver sinusoid, splenic marginal zone and red pulp and perisinusoidal macrophage protrusions in the bone marrow (BM) directly phagocytose BBPs in the blood as an innate immune response. The liver, spleen and BM thereby work together as the blood defence system (BDS) in response to BBPs by exerting their different immunological roles. The liver removes the vast majority of these invading organisms via innate immunity, but their complete elimination is not possible without the actions of antibodies. Splenic marginal zone B cells promptly produce IgM and IgG antibodies against BBPs. The splenic marginal zone transports antigenic information from the innate to the adaptive immune systems. The white pulp of the spleen functions as adaptive immune tissue and produces specific and high‐affinity antibodies with an immune memory against BBPs. The BM works to maintain immune memory by supporting the survival of memory B cells, memory T cells and long‐lived plasma cells (LLPCs), all of which have dedicated niches. Furthermore, BM perisinusoidal naïve follicular B cells promptly produce IgM antibodies against BBPs in the BM sinusoid and the IgG memory B cells residing in the BM rapidly transform to plasma cells which produce high‐affinity IgG antibodies upon reinfection. This review describes the complete immune defence characteristics of the BDS against BBPs through the collaboration of the liver, spleen and BM with combined different immunological roles.
血源性病原体（BBP）感染可迅速发展为危及生命的败血症，因此必须由宿主的免疫系统及时清除。肝窦、脾边缘区和红髓的血管内巨噬细胞以及骨髓（BM）窦周的巨噬细胞突起直接吞噬血液中的 BBP，这是一种先天性免疫反应。因此，肝脏、脾脏和骨髓作为血液防御系统（BDS），通过发挥各自不同的免疫作用，共同应对 BBPs。肝脏通过先天性免疫清除这些入侵生物的绝大部分，但如果没有抗体的作用，就不可能完全清除它们。脾边缘区 B 细胞会迅速产生针对 BBPs 的 IgM 和 IgG 抗体。脾边缘区将抗原信息从先天性免疫系统传递到适应性免疫系统。脾脏白髓作为适应性免疫组织，产生特异性和高亲和性抗体，对 BBPs 具有免疫记忆。基础细胞膜通过支持记忆 B 细胞、记忆 T 细胞和长寿命浆细胞（LLPCs）的存活来维持免疫记忆，所有这些细胞都有专门的龛位。此外，BM 窦状体周围的幼稚滤泡 B 细胞会迅速产生针对 BBPs 的 IgM 抗体，驻留在 BM 中的 IgG 记忆 B 细胞会迅速转化为浆细胞，在再次感染时产生高亲和性 IgG 抗体。本综述描述了 BDS 通过肝脏、脾脏和 BM 的协作，结合不同的免疫学作用，对 BBPs 的完整免疫防御特征。
{"title":"Blood defense system – Proposal for a new concept of an immune system against blood borne pathogens comprising the liver, spleen and bone marrow","authors":"Makoto Kashimura","doi":"10.1111/sji.13363","DOIUrl":"https://doi.org/10.1111/sji.13363","url":null,"abstract":"Blood‐borne pathogen (BBP) infections can rapidly progress to life‐threatening sepsis and must therefore be promptly eliminated by the host's immune system. Intravascular macrophages of the liver sinusoid, splenic marginal zone and red pulp and perisinusoidal macrophage protrusions in the bone marrow (BM) directly phagocytose BBPs in the blood as an innate immune response. The liver, spleen and BM thereby work together as the blood defence system (BDS) in response to BBPs by exerting their different immunological roles. The liver removes the vast majority of these invading organisms via innate immunity, but their complete elimination is not possible without the actions of antibodies. Splenic marginal zone B cells promptly produce IgM and IgG antibodies against BBPs. The splenic marginal zone transports antigenic information from the innate to the adaptive immune systems. The white pulp of the spleen functions as adaptive immune tissue and produces specific and high‐affinity antibodies with an immune memory against BBPs. The BM works to maintain immune memory by supporting the survival of memory B cells, memory T cells and long‐lived plasma cells (LLPCs), all of which have dedicated niches. Furthermore, BM perisinusoidal naïve follicular B cells promptly produce IgM antibodies against BBPs in the BM sinusoid and the IgG memory B cells residing in the BM rapidly transform to plasma cells which produce high‐affinity IgG antibodies upon reinfection. This review describes the complete immune defence characteristics of the BDS against BBPs through the collaboration of the liver, spleen and BM with combined different immunological roles.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140046051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Libo Ouyang, Keying Jing, Chunkai Zhu, Rong Wang, Peiming Zheng
The presence of autoantibodies is closely associated with the occurrence and development of cancer. Autoantibodies can be used as biomarkers for early breast cancer diagnosis. However, the relationship between autoantibodies and the prognosis of breast cancer patients remains elusive. This retrospective study aimed to investigate the correlation between the presence of autoantibodies and outcomes in breast cancer patients. This study included a total of 155 patients from People's Hospital of Henan University (Zhengzhou, China) who were diagnosed with breast cancer from January 2017 to December 2021. The enrolled patients' clinicopathological features were collected, and 88 patients were ultimately involved in the analysis. Univariate and multivariate Cox regression analyses were performed to search for the risk factors related to the poor prognosis of breast cancer patients. The association between the presence of autoantibodies and patients' survival was analysed using Kaplan–Meier curves. After screening, there were 38 autoantibody‐positive cases and 50 autoantibody‐negative cases. Breast cancer patients with autoantibody‐positive had a 57% lower risk of death compared with autoantibody‐negative patients. Multivariate Cox regression analysis indicated that the presence of autoantibody could be a potential prognostic predictor for breast cancer, independent of age, histological grade, pathological classification, clinical stage, and the expression levels of hormonal receptors. In addition, autoantibody‐positive breast cancer patients had longer progression‐free survival and overall survival compared with autoantibody‐negative cases. Positive autoantibody was found as an independent biomarker of better prognosis in breast cancer patients, providing a new strategy for the prognostic assessment of breast cancer patients.
{"title":"The presence of autoantibodies as a potential prognostic biomarker for breast cancer","authors":"Libo Ouyang, Keying Jing, Chunkai Zhu, Rong Wang, Peiming Zheng","doi":"10.1111/sji.13365","DOIUrl":"https://doi.org/10.1111/sji.13365","url":null,"abstract":"The presence of autoantibodies is closely associated with the occurrence and development of cancer. Autoantibodies can be used as biomarkers for early breast cancer diagnosis. However, the relationship between autoantibodies and the prognosis of breast cancer patients remains elusive. This retrospective study aimed to investigate the correlation between the presence of autoantibodies and outcomes in breast cancer patients. This study included a total of 155 patients from People's Hospital of Henan University (Zhengzhou, China) who were diagnosed with breast cancer from January 2017 to December 2021. The enrolled patients' clinicopathological features were collected, and 88 patients were ultimately involved in the analysis. Univariate and multivariate Cox regression analyses were performed to search for the risk factors related to the poor prognosis of breast cancer patients. The association between the presence of autoantibodies and patients' survival was analysed using Kaplan–Meier curves. After screening, there were 38 autoantibody‐positive cases and 50 autoantibody‐negative cases. Breast cancer patients with autoantibody‐positive had a 57% lower risk of death compared with autoantibody‐negative patients. Multivariate Cox regression analysis indicated that the presence of autoantibody could be a potential prognostic predictor for breast cancer, independent of age, histological grade, pathological classification, clinical stage, and the expression levels of hormonal receptors. In addition, autoantibody‐positive breast cancer patients had longer progression‐free survival and overall survival compared with autoantibody‐negative cases. Positive autoantibody was found as an independent biomarker of better prognosis in breast cancer patients, providing a new strategy for the prognostic assessment of breast cancer patients.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140002270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zsuzsa Huszenicza, Brian C. Gilmour, Lise Koll, Hanna Kjelstrup, Hanna Chan, Vibeke Sundvold, Stine Granum, Anne Spurkland
Adapter proteins are flexible and dynamic modulators of cellular signalling that are important for immune cell function. One of these, the T-cell-specific adapter protein (TSAd), interacts with the non-receptor tyrosine kinases Src and Lck of the Src family kinases (SFKs) and Itk of the Tec family kinases (TFKs). Three tyrosine residues in the TSAd C-terminus are phosphorylated by Lck and serve as docking sites for the Src homology 2 (SH2) domains of Src and Lck. The TSAd proline-rich region (PRR) binds to the Src homology 3 (SH3) domains found in Lck, Src and Itk. Despite known interactors, the role TSAd plays in cellular signalling remains largely unknown. TSAd's ability to bind both SFKs and TFKs may point to its function as a general scaffold for both kinase families. Using GST-pulldown as well as peptide array experiments, we found that both the SH2 and SH3 domains of the SFKs Fyn and Hck, as well as the TFKs Tec and Txk, interact with TSAd. This contrasts with Itk, which interacts with TSAd only through its SH3 domain. Although our analysis showed that TSAd is both co-expressed and may interact with Fyn, we were unable to co-precipitate Fyn with TSAd from Jurkat cells, as detected by Western blotting and affinity purification mass spectrometry. This may suggest that TSAd-Fyn interaction in intact cells may be limited by other factors, such as the subcellular localization of the two molecules or the co-expression of competing binding partners.
{"title":"Interaction of T-cell-specific adapter protein with Src- and Tec-family kinases","authors":"Zsuzsa Huszenicza, Brian C. Gilmour, Lise Koll, Hanna Kjelstrup, Hanna Chan, Vibeke Sundvold, Stine Granum, Anne Spurkland","doi":"10.1111/sji.13358","DOIUrl":"https://doi.org/10.1111/sji.13358","url":null,"abstract":"Adapter proteins are flexible and dynamic modulators of cellular signalling that are important for immune cell function. One of these, the T-cell-specific adapter protein (TSAd), interacts with the non-receptor tyrosine kinases Src and Lck of the Src family kinases (SFKs) and Itk of the Tec family kinases (TFKs). Three tyrosine residues in the TSAd C-terminus are phosphorylated by Lck and serve as docking sites for the Src homology 2 (SH2) domains of Src and Lck. The TSAd proline-rich region (PRR) binds to the Src homology 3 (SH3) domains found in Lck, Src and Itk. Despite known interactors, the role TSAd plays in cellular signalling remains largely unknown. TSAd's ability to bind both SFKs and TFKs may point to its function as a general scaffold for both kinase families. Using GST-pulldown as well as peptide array experiments, we found that both the SH2 and SH3 domains of the SFKs Fyn and Hck, as well as the TFKs Tec and Txk, interact with TSAd. This contrasts with Itk, which interacts with TSAd only through its SH3 domain. Although our analysis showed that TSAd is both co-expressed and may interact with Fyn, we were unable to co-precipitate Fyn with TSAd from Jurkat cells, as detected by Western blotting and affinity purification mass spectrometry. This may suggest that TSAd-Fyn interaction in intact cells may be limited by other factors, such as the subcellular localization of the two molecules or the co-expression of competing binding partners.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charles W. Armitage, Emily R. Bryan, Logan Trim, Ella Palframan, Lucas Wager, Kenneth W. Beagley, Alison J. Carey
Chlamydia trachomatis infection is the leading cause of bacterial urogenital infection and has been demonstrated to drive inflammation and scarring of the reproductive tract. Recent studies have identified key triggers of proinflammatory adaptive immune responses driven by innate leukocytes and epithelia driving immunopathology. Utilizing chimeric mouse models, we investigated the definitive source and role of IL17 and IL17 signalling receptors during early Chlamydia muridarum infection of the female urogenital tract. Bone marrow transplants from wild-type (WT) and IL17A−/− mice to recipients demonstrated equivocal infection kinetics in the reproductive tract, but interestingly, adoptive transfer of IL17A−/− immune cells to WT recipients resulted in no infertility, suggesting a haematopoietic (as opposed to tissue) source of IL17 driving immunopathology. To further delineate the role of IL17 in immunopathology, we infected WT and IL17 receptor A (IL17RA)−/− female mice and observed a significant reduction in immunopathology in IL17RA−/− mice. WT bone marrow transplants to IL17RA−/− recipient mice prevented hydrosalpinx, suggesting signalling through IL17RA drives immunopathology. Furthermore, early chemical inhibition of IL17 signalling significantly reduced hydrosalpinx, suggesting IL17 acts as an innate driver of disease. Early during the infection, IL17 was produced by γδ T cells in the cervico-vagina, but more importantly, by neutrophils at the site of infertility in the oviducts. Taken together, these data suggest innate production of IL17 by haematopoietic leukocytes drives immunopathology in the epithelia during early C. muridarum infection of the female reproductive tract.
{"title":"Haematopoietic innate interleukin 17A production drives immunopathology in female mouse genital Chlamydia muridarum infection","authors":"Charles W. Armitage, Emily R. Bryan, Logan Trim, Ella Palframan, Lucas Wager, Kenneth W. Beagley, Alison J. Carey","doi":"10.1111/sji.13359","DOIUrl":"https://doi.org/10.1111/sji.13359","url":null,"abstract":"<i>Chlamydia trachomatis</i> infection is the leading cause of bacterial urogenital infection and has been demonstrated to drive inflammation and scarring of the reproductive tract. Recent studies have identified key triggers of proinflammatory adaptive immune responses driven by innate leukocytes and epithelia driving immunopathology. Utilizing chimeric mouse models, we investigated the definitive source and role of IL17 and IL17 signalling receptors during early <i>Chlamydia muridarum</i> infection of the female urogenital tract. Bone marrow transplants from wild-type (WT) and IL17A<sup>−/−</sup> mice to recipients demonstrated equivocal infection kinetics in the reproductive tract, but interestingly, adoptive transfer of IL17A<sup>−/−</sup> immune cells to WT recipients resulted in no infertility, suggesting a haematopoietic (as opposed to tissue) source of IL17 driving immunopathology. To further delineate the role of IL17 in immunopathology, we infected WT and IL17 receptor A (IL17RA)<sup>−/−</sup> female mice and observed a significant reduction in immunopathology in IL17RA<sup>−/−</sup> mice. WT bone marrow transplants to IL17RA<sup>−/−</sup> recipient mice prevented hydrosalpinx, suggesting signalling through IL17RA drives immunopathology. Furthermore, early chemical inhibition of IL17 signalling significantly reduced hydrosalpinx, suggesting IL17 acts as an innate driver of disease. Early during the infection, IL17 was produced by γδ T cells in the cervico-vagina, but more importantly, by neutrophils at the site of infertility in the oviducts. Taken together, these data suggest innate production of IL17 by haematopoietic leukocytes drives immunopathology in the epithelia during early <i>C. muridarum</i> infection of the female reproductive tract.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139517985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhongling Dai, Zhande Gong, Cui Wang, WeiXiang Long, Duo Liu, Haijun Zhang, Aihua Lei
Group 2 innate lymphoid cells (ILC2s) are a type of innate immune cells that produce a large amount of IL-5 and IL-13 and two cytokines that are crucial for various processes such as allergic airway inflammation, tissue repair and tissue homeostasis. It is known that damaged epithelial-derived alarmins, such as IL-33, IL-25 and thymic stromal lymphopoietin (TSLP), are the predominant ILC2 activators that mediate the production of type 2 cytokines. In recent years, abundant studies have found that many factors can regulate ILC2 development and function. Hormones synthesized by the body's endocrine glands or cells play an important role in immune response. Notably, ILC2s express hormone receptors and their proliferation and function can be modulated by multiple hormones during allergic airway inflammation. Here, we summarize the effects of multiple hormones on ILC2-driven allergic airway inflammation and discuss the underlying mechanisms and potential therapeutic significance.
{"title":"The role of hormones in ILC2-driven allergic airway inflammation","authors":"Zhongling Dai, Zhande Gong, Cui Wang, WeiXiang Long, Duo Liu, Haijun Zhang, Aihua Lei","doi":"10.1111/sji.13357","DOIUrl":"https://doi.org/10.1111/sji.13357","url":null,"abstract":"Group 2 innate lymphoid cells (ILC2s) are a type of innate immune cells that produce a large amount of IL-5 and IL-13 and two cytokines that are crucial for various processes such as allergic airway inflammation, tissue repair and tissue homeostasis. It is known that damaged epithelial-derived alarmins, such as IL-33, IL-25 and thymic stromal lymphopoietin (TSLP), are the predominant ILC2 activators that mediate the production of type 2 cytokines. In recent years, abundant studies have found that many factors can regulate ILC2 development and function. Hormones synthesized by the body's endocrine glands or cells play an important role in immune response. Notably, ILC2s express hormone receptors and their proliferation and function can be modulated by multiple hormones during allergic airway inflammation. Here, we summarize the effects of multiple hormones on ILC2-driven allergic airway inflammation and discuss the underlying mechanisms and potential therapeutic significance.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139517811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoqin Wang, Yinsha Miao, Jinghui Shen, Dandan Li, Xinyue Deng, Chengcheng Yang, Yanhong Ji, ZhiJun Dai, Yunfeng Ma
In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in-depth research. Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra-tumoural T-cell ratios or in the functionality of T-cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8+ T cells by elevating IFN-γ and granzyme B production. Our compelling evidence highlights that combination therapy more effectively inhibited tumour growth and prolonged survival compared to either monotherapy, thus mitigating the limitations intrinsic to single-agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro-immunogenic conditions. This assertion is backed by a raised CD8+/CD4+ T-cell ratio and a decrease in immunosuppressive MDSC and Treg cell populations. On the mechanistic front, the synergistic therapy amplified expression levels of CXCL13 in tumours, subsequently facilitating T-cell ingress into the tumour setting. In summary, our findings advocate for integrated therapy as a potent mechanism for surmounting PD1 antibody resistance, capitalizing on improved T-cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti-tumour immunity through the application of innovative therapeutic strategies.
鉴于某些患者群体对 PD1 抗体治疗的耐药性不断增加，因此亟需进行深入研究。我们的研究采用小鼠 CT26/MUC1 结肠癌模型，评估了 MUC1 DNA 疫苗和 PD1 抗体在克服 PD1 抗药性方面的协同作用。在单独治疗时，PD1 抗体对肿瘤生长没有影响。此外，瘤内 T 细胞比例或 T 细胞功能也没有发生变化。相比之下，单独注射 MUC1 DNA 疫苗可通过提高 IFN-γ 和颗粒酶 B 的产生，显著增强 CD8+ T 细胞的细胞毒性。我们令人信服的证据表明，与单一疗法相比，联合疗法能更有效地抑制肿瘤生长并延长生存期，从而缓解了单药疗法固有的局限性。肿瘤微环境的显著改变推动了疗效的增强，使其向有利于免疫原性的条件倾斜。CD8+/CD4+ T细胞比率的提高以及免疫抑制性MDSC和Treg细胞群的减少都证明了这一点。在机理方面，协同疗法提高了肿瘤中CXCL13的表达水平，从而促进T细胞进入肿瘤环境。总之，我们的研究结果主张将综合疗法作为克服 PD1 抗体耐药性的一种有效机制，利用改善的 T 细胞功能和浸润。这项研究为通过应用创新治疗策略增强抗肿瘤免疫力提供了重要的视角。
{"title":"Unlocking PD-1 antibody resistance: The MUC1 DNA vaccine augments CD8+ T cell infiltration and attenuates tumour suppression","authors":"Xiaoqin Wang, Yinsha Miao, Jinghui Shen, Dandan Li, Xinyue Deng, Chengcheng Yang, Yanhong Ji, ZhiJun Dai, Yunfeng Ma","doi":"10.1111/sji.13356","DOIUrl":"https://doi.org/10.1111/sji.13356","url":null,"abstract":"In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in-depth research. Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra-tumoural T-cell ratios or in the functionality of T-cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8<sup>+</sup> T cells by elevating IFN-γ and granzyme B production. Our compelling evidence highlights that combination therapy more effectively inhibited tumour growth and prolonged survival compared to either monotherapy, thus mitigating the limitations intrinsic to single-agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro-immunogenic conditions. This assertion is backed by a raised CD8<sup>+</sup>/CD4<sup>+</sup> T-cell ratio and a decrease in immunosuppressive MDSC and Treg cell populations. On the mechanistic front, the synergistic therapy amplified expression levels of CXCL13 in tumours, subsequently facilitating T-cell ingress into the tumour setting. In summary, our findings advocate for integrated therapy as a potent mechanism for surmounting PD1 antibody resistance, capitalizing on improved T-cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti-tumour immunity through the application of innovative therapeutic strategies.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139518034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ke Zhu, Chen Liu, Xiaofang Guo, Xuting Zhang, Jiaxin Xie, Songmiao Xie, Qing Qi, Bin Yang
Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Vascular damage is one of the important features of SSc, which affects the progression and prognosis of the disease. MiR-126-3p is an important microRNA (miRNA) that regulates vascular structure and function, which can be transported through exosomes. However, the role of miR-126-3p in vascular damage in SSc is still unclear. Therefore, we focused on the connection between miR-126-3p and vascular damage in SSc, as well as investigated the potential role of miR-126-3p in vascular damage in SSc. First, this study successfully extracted extracellular vesicles from clinical plasma samples and characterized the exosomes within them. Then, we predicted and screened the target pathway mammalian/mechanistic target of rapamycin (mTOR) and the target gene SLC7A5 of miR-126-3p through online databases. Next, we constructed SSc mice for in vivo studies. The results showed that the expression of miR-126-3p was decreased in the plasma exosomes, while the SLC7A5 expression, autophagy, and lipid peroxidation were increased in the aorta. Luciferase reporter gene assays demonstrated that miR-126-3p can bind to SLC7A5, resulting in a decrease in its expression. In vitro experiments have shown that exosomal miR-126-3p can be internalized by human umbilical vein endothelial cells (HUVECs). The miR-126-3p group exhibited enhanced cell viability and tube formation ability, along with increased expression of the vascular formation marker CD31. Additionally, miR-126-3p downregulated the protein expression of SLC7A5 and LC3 in HUVECs, while upregulating the protein expression of mTOR, P62, PPARγ, and CPT-1. However, the effects of miR-126-3p on HUVECs were counteracted by mTOR inhibitors and enhanced by mTOR activators. The results indicated that exosomal miR-126-3p has the potential to protect against vascular injury in SSc by regulating the SLC7A5/mTOR signalling pathway in HUVECs.
{"title":"Exosomal miR-126-3p: Potential protection against vascular damage by regulating the SLC7A5/mTOR Signalling pathway in human umbilical vein endothelial cells","authors":"Ke Zhu, Chen Liu, Xiaofang Guo, Xuting Zhang, Jiaxin Xie, Songmiao Xie, Qing Qi, Bin Yang","doi":"10.1111/sji.13354","DOIUrl":"https://doi.org/10.1111/sji.13354","url":null,"abstract":"Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Vascular damage is one of the important features of SSc, which affects the progression and prognosis of the disease. MiR-126-3p is an important microRNA (miRNA) that regulates vascular structure and function, which can be transported through exosomes. However, the role of miR-126-3p in vascular damage in SSc is still unclear. Therefore, we focused on the connection between miR-126-3p and vascular damage in SSc, as well as investigated the potential role of miR-126-3p in vascular damage in SSc. First, this study successfully extracted extracellular vesicles from clinical plasma samples and characterized the exosomes within them. Then, we predicted and screened the target pathway mammalian/mechanistic target of rapamycin (mTOR) and the target gene SLC7A5 of miR-126-3p through online databases. Next, we constructed SSc mice for in vivo studies. The results showed that the expression of miR-126-3p was decreased in the plasma exosomes, while the SLC7A5 expression, autophagy, and lipid peroxidation were increased in the aorta. Luciferase reporter gene assays demonstrated that miR-126-3p can bind to SLC7A5, resulting in a decrease in its expression. In vitro experiments have shown that exosomal miR-126-3p can be internalized by human umbilical vein endothelial cells (HUVECs). The miR-126-3p group exhibited enhanced cell viability and tube formation ability, along with increased expression of the vascular formation marker CD31. Additionally, miR-126-3p downregulated the protein expression of SLC7A5 and LC3 in HUVECs, while upregulating the protein expression of mTOR, P62, PPARγ, and CPT-1. However, the effects of miR-126-3p on HUVECs were counteracted by mTOR inhibitors and enhanced by mTOR activators. The results indicated that exosomal miR-126-3p has the potential to protect against vascular injury in SSc by regulating the SLC7A5/mTOR signalling pathway in HUVECs.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139498207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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