Pub Date : 2024-08-12eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e32
Bo-Gyu Kim, Hoon Sik Choi, Yong-Ho Choe, Hyun Min Jeon, Ji Yeon Heo, Yun-Hong Cheon, Ki Mun Kang, Sang-Il Lee, Bae Kwon Jeong, Mingyo Kim
Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19+ B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.
{"title":"Low-Dose Radiotherapy Attenuates Experimental Autoimmune Arthritis by Inducing Apoptosis of Lymphocytes and Fibroblast-Like Synoviocytes.","authors":"Bo-Gyu Kim, Hoon Sik Choi, Yong-Ho Choe, Hyun Min Jeon, Ji Yeon Heo, Yun-Hong Cheon, Ki Mun Kang, Sang-Il Lee, Bae Kwon Jeong, Mingyo Kim","doi":"10.4110/in.2024.24.e32","DOIUrl":"10.4110/in.2024.24.e32","url":null,"abstract":"<p><p>Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4<sup>+</sup> T and B220<sup>+</sup> B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4<sup>+</sup> T and CD19<sup>+</sup> B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e31
Manisha Naskar, Hae Woong Choi
Urinary tract infections (UTIs) represent one of the most prevalent bacterial infections globally, manifesting in diverse clinical phenotypes with varying degrees of severity and complications. The mechanisms underlying UTIs are gradually being elucidated, leading to an enhanced understanding of the immune responses involved. Innate immune cells play a crucial defensive role against uropathogenic bacteria through various mechanisms. Despite their significant contributions to host defense, these cells often fail to achieve complete clearance of uropathogens, necessitating the frequent prescription of antibiotics for UTI patients. However, the persistence of infections and related pathological symptoms in the absence of innate immune cells in animal models underscore the importance of innate immunity in UTIs. Therefore, the host protective functions of innate immune cells, including neutrophils, macrophages, mast cells, NK cells, innate lymphoid cells, and γδ T cells, are delicately coordinated and timely regulated by a variety of cytokines to ensure successful pathogen clearance.
尿路感染(UTI)是全球最常见的细菌感染之一,临床表现多种多样,严重程度和并发症也各不相同。尿路感染的发病机制正逐渐被阐明,从而加深了人们对相关免疫反应的了解。先天性免疫细胞通过各种机制对尿路致病菌发挥着重要的防御作用。尽管先天性免疫细胞对宿主防御做出了重要贡献,但它们往往无法完全清除尿路病原体,因此尿路感染患者必须经常使用抗生素。然而,在动物模型中,在先天性免疫细胞缺失的情况下,感染和相关病理症状仍会持续,这凸显了先天性免疫在UTI 中的重要性。因此,先天性免疫细胞(包括中性粒细胞、巨噬细胞、肥大细胞、NK 细胞、先天性淋巴细胞和 γδ T 细胞)对宿主的保护功能受到各种细胞因子的微妙协调和及时调控,以确保成功清除病原体。
{"title":"A Dynamic Interplay of Innate Immune Responses During Urinary Tract Infection.","authors":"Manisha Naskar, Hae Woong Choi","doi":"10.4110/in.2024.24.e31","DOIUrl":"10.4110/in.2024.24.e31","url":null,"abstract":"<p><p>Urinary tract infections (UTIs) represent one of the most prevalent bacterial infections globally, manifesting in diverse clinical phenotypes with varying degrees of severity and complications. The mechanisms underlying UTIs are gradually being elucidated, leading to an enhanced understanding of the immune responses involved. Innate immune cells play a crucial defensive role against uropathogenic bacteria through various mechanisms. Despite their significant contributions to host defense, these cells often fail to achieve complete clearance of uropathogens, necessitating the frequent prescription of antibiotics for UTI patients. However, the persistence of infections and related pathological symptoms in the absence of innate immune cells in animal models underscore the importance of innate immunity in UTIs. Therefore, the host protective functions of innate immune cells, including neutrophils, macrophages, mast cells, NK cells, innate lymphoid cells, and γδ T cells, are delicately coordinated and timely regulated by a variety of cytokines to ensure successful pathogen clearance.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e30
Jin Soo Joo, Dongeun Lee, Jun Young Hong
Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.
妊娠是一个免疫学悖论,母体免疫系统必须耐受表达父源抗体的半异体胎儿。几十年来积累的证据表明,成功妊娠需要积极发展强大的免疫耐受机制。本综述概述了建立胎儿-母体耐受性的多层次过程,包括胎盘的物理屏障、趋化因子介导的白细胞迁移受限、缺乏足够的同种抗原呈递、存在免疫抑制调节性 T 细胞和耐受性蜕膜自然杀伤细胞、免疫检查点分子的表达、赋予免疫逃避功能的特定糖基化模式以及独特的代谢/激素调节。有趣的是,使胎儿产生耐受性的许多策略与癌细胞促进血管生成、侵袭和免疫逃逸的策略相似。因此,进一步阐明胎儿-母体耐受性的机理基础可为开发新型癌症免疫疗法以及了解与耐受性失调过程相关的妊娠并发症的发病机制提供有益的启示。
{"title":"Multi-Layered Mechanisms of Immunological Tolerance at the Maternal-Fetal Interface.","authors":"Jin Soo Joo, Dongeun Lee, Jun Young Hong","doi":"10.4110/in.2024.24.e30","DOIUrl":"10.4110/in.2024.24.e30","url":null,"abstract":"<p><p>Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-27eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e29
Thamer A Hamdan
NK cells belong to innate lymphoid cells and able to eliminate infected cells and tumor cells. NK cells play a valuable role in controlling viral infections. Also, they have the potential to shape the adaptive immunity via a unique crosstalk with the different immune cells. Murine models are important tools for delineating the immunological phenomena in viral infection. To decipher the immunological virus-host interactions, two major infection models are being investigated in mice regarding NK cell-mediated recognition: murine cytomegalovirus (MCMV) and lymphocytic choriomeningitis virus (LCMV). In this review, we recapitulate recent findings regarding the multifaceted role of NK cells in controlling LCMV and MCMV infections and outline the exquisite interplay between NK cells and other immune cells in these two settings. Considering that, infections with MCMV and LCMV recapitulates many physiopathological characteristics of human cytomegalovirus infection and chronic virus infections respectively, this study will extend our understanding of NK cells biology in interactions between the virus and its natural host.
NK 细胞属于先天性淋巴细胞,能够清除受感染的细胞和肿瘤细胞。NK 细胞在控制病毒感染方面发挥着重要作用。此外,NK 细胞还能通过与不同免疫细胞之间的独特串扰,形成适应性免疫。小鼠模型是描述病毒感染免疫现象的重要工具。为了破译病毒与宿主之间的免疫学相互作用,目前正在小鼠中研究 NK 细胞介导识别的两种主要感染模型:鼠巨细胞病毒(MCMV)和淋巴细胞性脉络膜炎病毒(LCMV)。在这篇综述中,我们回顾了有关 NK 细胞在控制 LCMV 和 MCMV 感染中的多方面作用的最新发现,并概述了 NK 细胞和其他免疫细胞在这两种情况下的微妙相互作用。考虑到 MCMV 和 LCMV 感染分别再现了人类巨细胞病毒感染和慢性病毒感染的许多生理病理特征,本研究将扩展我们对 NK 细胞在病毒与其自然宿主相互作用中的生物学作用的理解。
{"title":"The Multifaceted Roles of NK Cells in the Context of Murine Cytomegalovirus and Lymphocytic Choriomeningitis Virus Infections.","authors":"Thamer A Hamdan","doi":"10.4110/in.2024.24.e29","DOIUrl":"10.4110/in.2024.24.e29","url":null,"abstract":"<p><p>NK cells belong to innate lymphoid cells and able to eliminate infected cells and tumor cells. NK cells play a valuable role in controlling viral infections. Also, they have the potential to shape the adaptive immunity via a unique crosstalk with the different immune cells. Murine models are important tools for delineating the immunological phenomena in viral infection. To decipher the immunological virus-host interactions, two major infection models are being investigated in mice regarding NK cell-mediated recognition: murine cytomegalovirus (MCMV) and lymphocytic choriomeningitis virus (LCMV). In this review, we recapitulate recent findings regarding the multifaceted role of NK cells in controlling LCMV and MCMV infections and outline the exquisite interplay between NK cells and other immune cells in these two settings. Considering that, infections with MCMV and LCMV recapitulates many physiopathological characteristics of human cytomegalovirus infection and chronic virus infections respectively, this study will extend our understanding of NK cells biology in interactions between the virus and its natural host.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e28
Wooseob Kim
Vaccines are the most effective intervention currently available, offering protective immunity against targeted pathogens. The emergence of the coronavirus disease 2019 pandemic has prompted rapid development and deployment of lipid nanoparticle encapsulated, mRNA-based vaccines. While these vaccines have demonstrated remarkable immunogenicity, concerns persist regarding their ability to confer durable protective immunity to continuously evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. This review focuses on human B cell responses induced by SARS-CoV-2 mRNA vaccination, with particular emphasis on the crucial role of germinal center reactions in shaping enduring protective immunity. Additionally, we explored observations of immunological imprinting and dynamics of recalled pre-existing immunity following variants of concern-based booster vaccination. Insights from this review contribute to comprehensive understanding B cell responses to mRNA vaccination in humans, thereby refining vaccination strategies for optimal and sustained protection against evolving coronavirus variants.
疫苗是目前最有效的干预措施,可提供针对目标病原体的保护性免疫。2019 年冠状病毒疾病大流行的出现,促使基于 mRNA 的脂质纳米颗粒封装疫苗的快速开发和部署。虽然这些疫苗已显示出显著的免疫原性,但人们仍然担心它们能否对不断演变的严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)变种产生持久的保护性免疫。本综述重点探讨接种 SARS-CoV-2 mRNA 疫苗诱导的人类 B 细胞反应,特别强调生殖中心反应在形成持久保护性免疫力中的关键作用。此外,我们还探讨了免疫印记的观察结果,以及在接种基于关注的变异株加强免疫后回忆原有免疫力的动态变化。本综述中的观点有助于全面了解人类 B 细胞对 mRNA 疫苗接种的反应,从而完善疫苗接种策略,针对不断演变的冠状病毒变种提供最佳和持续的保护。
{"title":"Germinal Center Response to mRNA Vaccination and Impact of Immunological Imprinting on Subsequent Vaccination.","authors":"Wooseob Kim","doi":"10.4110/in.2024.24.e28","DOIUrl":"10.4110/in.2024.24.e28","url":null,"abstract":"<p><p>Vaccines are the most effective intervention currently available, offering protective immunity against targeted pathogens. The emergence of the coronavirus disease 2019 pandemic has prompted rapid development and deployment of lipid nanoparticle encapsulated, mRNA-based vaccines. While these vaccines have demonstrated remarkable immunogenicity, concerns persist regarding their ability to confer durable protective immunity to continuously evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. This review focuses on human B cell responses induced by SARS-CoV-2 mRNA vaccination, with particular emphasis on the crucial role of germinal center reactions in shaping enduring protective immunity. Additionally, we explored observations of immunological imprinting and dynamics of recalled pre-existing immunity following variants of concern-based booster vaccination. Insights from this review contribute to comprehensive understanding B cell responses to mRNA vaccination in humans, thereby refining vaccination strategies for optimal and sustained protection against evolving coronavirus variants.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24eCollection Date: 2024-06-01DOI: 10.4110/in.2024.24.e27
Hyo-Min Park, Jae-Young Park, Na-Yeon Kim, Hyemoon Kim, Hong-Gyum Kim, Dong-Ju Son, Jin Tae Hong, Do-Young Yoon
The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1β, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFβ, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.
{"title":"Recombinant Human IL-32θ Induces Polarization Into M1-like Macrophage in Human Monocytic Cells.","authors":"Hyo-Min Park, Jae-Young Park, Na-Yeon Kim, Hyemoon Kim, Hong-Gyum Kim, Dong-Ju Son, Jin Tae Hong, Do-Young Yoon","doi":"10.4110/in.2024.24.e27","DOIUrl":"10.4110/in.2024.24.e27","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an <i>Escherichia coli</i> expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1β, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFβ, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24eCollection Date: 2024-06-01DOI: 10.4110/in.2024.24.e26
Jisu Kim, Jee Yeon Choi, Hyeyoung Min, Kwang Woo Hwang
Recent advancements in various technologies have shed light on the critical role of metabolism in immune cells, paving the way for innovative disease treatment strategies through immunometabolism modulation. This review emphasizes the glucose metabolism of myeloid-derived suppressor cells (MDSCs), an emerging pivotal immunosuppressive factor especially within the tumor microenvironment. MDSCs, an immature and heterogeneous myeloid cell population, act as a double-edged sword by exacerbating tumors or mitigating inflammatory diseases through their immune-suppressive functions. Numerous recent studies have centered on glycolysis of MDSC, investigating the regulation of altered glycolytic pathways to manage diseases. However, the specific changes in MDSC glycolysis and their exact functions continue to be areas of ongoing discussion yet. In this paper, we review a range of current findings, including the latest research on the alteration of glycolysis in MDSCs, the consequential functional alterations in these cells, and the outcomes of attempts to modulate MDSC functions by regulating glycolysis. Ultimately, we will provide insights into whether these research efforts could be translated into clinical applications.
{"title":"Exploring the Potential of Glycolytic Modulation in Myeloid-Derived Suppressor Cells for Immunotherapy and Disease Management.","authors":"Jisu Kim, Jee Yeon Choi, Hyeyoung Min, Kwang Woo Hwang","doi":"10.4110/in.2024.24.e26","DOIUrl":"10.4110/in.2024.24.e26","url":null,"abstract":"<p><p>Recent advancements in various technologies have shed light on the critical role of metabolism in immune cells, paving the way for innovative disease treatment strategies through immunometabolism modulation. This review emphasizes the glucose metabolism of myeloid-derived suppressor cells (MDSCs), an emerging pivotal immunosuppressive factor especially within the tumor microenvironment. MDSCs, an immature and heterogeneous myeloid cell population, act as a double-edged sword by exacerbating tumors or mitigating inflammatory diseases through their immune-suppressive functions. Numerous recent studies have centered on glycolysis of MDSC, investigating the regulation of altered glycolytic pathways to manage diseases. However, the specific changes in MDSC glycolysis and their exact functions continue to be areas of ongoing discussion yet. In this paper, we review a range of current findings, including the latest research on the alteration of glycolysis in MDSCs, the consequential functional alterations in these cells, and the outcomes of attempts to modulate MDSC functions by regulating glycolysis. Ultimately, we will provide insights into whether these research efforts could be translated into clinical applications.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e25
Sung Hoon Jang, Joo Sung Shim, Jieun Kim, Eun Gyeol Shin, Jong Hwi Yoon, Lucy Eunju Lee, Ho-Keun Kwon, Jason Jungsik Song
Lupus is characterized by the autoantibodies against nuclear Ags, underscoring the importance of identifying the B cell subsets driving autoimmunity. Our research focused on the mitochondrial activity and CXCR4 expression in CD11c+ B cells from lupus patients after ex vivo stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c+ B cells in ODN-injected mice. Post-ex vivo ODN stimulation, we observed an increase in the proportion of CD11chi cells, with elevated mitochondrial activity and CXCR4 expression in CD11c+ B cells from lupus patients. In vivo experiments showed similar patterns, with TLR9 stimulation enhancing mitochondrial and CXCR4 activities in CD11chi B cells, leading to the generation of anti-dsDNA plasmablasts. The CXCR4 inhibitor AMD3100 and the mitochondrial complex I inhibitor IM156 significantly reduced the proportion of CD11c+ B cells and autoreactive plasmablasts. These results underscore the pivotal roles of mitochondria and CXCR4 in the production of autoreactive plasmablasts.
红斑狼疮的特征是针对核Ags的自身抗体,这就强调了识别驱动自身免疫的B细胞亚群的重要性。我们的研究重点是红斑狼疮患者的 CD11c+ B 细胞在体内外受到 TLR9 激动剂 CpG-寡脱氧核苷酸(ODN)刺激后的线粒体活性和 CXCR4 表达。我们还评估了注射 ODN 的小鼠 CD11c+ B 细胞的反应。在体外 ODN 刺激后,我们观察到 CD11chi 细胞比例增加,狼疮患者 CD11c+ B 细胞的线粒体活性和 CXCR4 表达升高。体内实验显示了类似的模式,TLR9刺激增强了CD11chi B细胞的线粒体和CXCR4活性,导致抗dsDNA浆细胞的产生。CXCR4 抑制剂 AMD3100 和线粒体复合体 I 抑制剂 IM156 能显著降低 CD11c+ B 细胞和自反应性浆细胞的比例。这些结果强调了线粒体和 CXCR4 在产生自反应性浆细胞中的关键作用。
{"title":"Mitochondria Activity and CXCR4 Collaboratively Promote the Differentiation of CD11c<sup>+</sup> B Cells Induced by TLR9 in Lupus.","authors":"Sung Hoon Jang, Joo Sung Shim, Jieun Kim, Eun Gyeol Shin, Jong Hwi Yoon, Lucy Eunju Lee, Ho-Keun Kwon, Jason Jungsik Song","doi":"10.4110/in.2024.24.e25","DOIUrl":"10.4110/in.2024.24.e25","url":null,"abstract":"<p><p>Lupus is characterized by the autoantibodies against nuclear Ags, underscoring the importance of identifying the B cell subsets driving autoimmunity. Our research focused on the mitochondrial activity and CXCR4 expression in CD11c<sup>+</sup> B cells from lupus patients after <i>ex vivo</i> stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c<sup>+</sup> B cells in ODN-injected mice. Post-<i>ex vivo</i> ODN stimulation, we observed an increase in the proportion of CD11c<sup>hi</sup> cells, with elevated mitochondrial activity and CXCR4 expression in CD11c<sup>+</sup> B cells from lupus patients. <i>In vivo</i> experiments showed similar patterns, with TLR9 stimulation enhancing mitochondrial and CXCR4 activities in CD11c<sup>hi</sup> B cells, leading to the generation of anti-dsDNA plasmablasts. The CXCR4 inhibitor AMD3100 and the mitochondrial complex I inhibitor IM156 significantly reduced the proportion of CD11c<sup>+</sup> B cells and autoreactive plasmablasts. These results underscore the pivotal roles of mitochondria and CXCR4 in the production of autoreactive plasmablasts.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e24
Eun-Hyeon Shim, Sae-Hae Kim, Doo-Jin Kim, Yong-Suk Jang
Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.
{"title":"Complement C5a Receptor Signaling in Macrophages Enhances Trained Immunity Through mTOR Pathway Activation.","authors":"Eun-Hyeon Shim, Sae-Hae Kim, Doo-Jin Kim, Yong-Suk Jang","doi":"10.4110/in.2024.24.e24","DOIUrl":"10.4110/in.2024.24.e24","url":null,"abstract":"<p><p>Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31eCollection Date: 2024-06-01DOI: 10.4110/in.2024.24.e23
Hyunseo Lim, Young Ho Choe, Jaeho Lee, Gi Eun Kim, Jin Won Hyun, Young-Min Hyun
Adipose tissue, well known for its endocrine function, plays an immunological role in the body. The inflamed adipose tissue under LPS-induced systemic inflammation is characterized by the dominance of pro-inflammatory immune cells, particularly neutrophils. Although migration of macrophages toward damaged or dead adipocytes to form a crown-like structure in inflamed adipose tissue has been revealed, the neutrophilic interaction with adipocytes or the extracellular matrix remains unknown. Here, we demonstrated the involvement of adhesion molecules, particularly integrin α6β1, of neutrophils in adipocytes or the extracellular matrix of inflamed adipose tissue interaction. These results suggest that disrupting the adhesion between adipose tissue components and neutrophils may govern the accumulation of excessive neutrophils in inflamed tissues, a prerequisite in developing anti-inflammatory therapeutics by inhibiting inflammatory immune cells.
{"title":"Neutrophil Migration Is Mediated by VLA-6 in the Inflamed Adipose Tissue.","authors":"Hyunseo Lim, Young Ho Choe, Jaeho Lee, Gi Eun Kim, Jin Won Hyun, Young-Min Hyun","doi":"10.4110/in.2024.24.e23","DOIUrl":"10.4110/in.2024.24.e23","url":null,"abstract":"<p><p>Adipose tissue, well known for its endocrine function, plays an immunological role in the body. The inflamed adipose tissue under LPS-induced systemic inflammation is characterized by the dominance of pro-inflammatory immune cells, particularly neutrophils. Although migration of macrophages toward damaged or dead adipocytes to form a crown-like structure in inflamed adipose tissue has been revealed, the neutrophilic interaction with adipocytes or the extracellular matrix remains unknown. Here, we demonstrated the involvement of adhesion molecules, particularly integrin α6β1, of neutrophils in adipocytes or the extracellular matrix of inflamed adipose tissue interaction. These results suggest that disrupting the adhesion between adipose tissue components and neutrophils may govern the accumulation of excessive neutrophils in inflamed tissues, a prerequisite in developing anti-inflammatory therapeutics by inhibiting inflammatory immune cells.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}