International immunology最新文献_第3页

The active form of vitamin D (calcitriol) promotes CXCR5 expression during follicular helper T cell differentiation. 维生素 D 的活性形式（钙三醇）可在滤泡辅助性 T 细胞分化过程中促进 CXCR5 的表达。

IF 4.8 4区医学

International immunology Pub Date : 2024-08-05 DOI: 10.1093/intimm/dxae045

Makoto Iwata, Ayumi Takada, Rei Sakamoto, Si-Young Song, Etsuro Ito

{"title":"The active form of vitamin D (calcitriol) promotes CXCR5 expression during follicular helper T cell differentiation.","authors":"Makoto Iwata, Ayumi Takada, Rei Sakamoto, Si-Young Song, Etsuro Ito","doi":"10.1093/intimm/dxae045","DOIUrl":"https://doi.org/10.1093/intimm/dxae045","url":null,"abstract":"Follicular helper T (Tfh) cells promote B cell differentiation and antibody production in the B cell follicles of secondary lymphoid organs. Tfh cells express their signature transcription factor BCL6, interleukin (IL)-21, and surface molecules including inducible T cell costimulator, programmed cell death-1 (PD-1), and the chemokine receptor CXCR5. Migration of Tfh cells to B cell follicles largely depends on the CXCR5 expression induced by interactions with antigen-presenting dendritic cells in the T cell area. How Tfh cells acquire sufficient levels of CXCR5 expression, however, has remained unclear. Using our in vitro culture system to generate CXCR5low Tfh-like cells from naïve CD4+ T cells with IL-6 in the absence of other cell types, we found that the active form of vitamin D, calcitriol, markedly enhanced CXCR5 expression after the release from persistent T cell receptor (TCR) stimulation. CH-223191, an aryl hydrocarbon receptor antagonist, further enhanced CXCR5 expression. IL-12 but not IL-4, in place of IL-6, also supported calcitriol to enhance CXCR5 expression even before the release from TCR stimulation, whereas the cell viability sharply decreased after the release. The Tfh-like cells generated with IL-6 and calcitriol exhibited chemotaxis towards CXCL13, expressed IL-21, and helped B cells to produce IgG antibodies in vitro more efficiently than Tfh-like cells generated without added calcitriol. Calcitriol injections into antigen-primed mice increased the proportion of CXCR5+PD-1+CD4+ cells in their lymphoid organs, and enhanced T cell entry into B-cell follicles. These results suggest that calcitriol promotes CXCR5 expression in developing Tfh cells and regulates their functional differentiation.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889117","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}

引用次数: 0

Pathogenesis of IgA nephropathy as a tissue-specific autoimmune disease. 作为一种组织特异性自身免疫疾病的 IgA 肾病的发病机制。

IF 4.8 4区医学

International immunology Pub Date : 2024-07-27 DOI: 10.1093/intimm/dxae047

Yoshihito Nihei, Daisuke Kitamura

{"title":"Pathogenesis of IgA nephropathy as a tissue-specific autoimmune disease.","authors":"Yoshihito Nihei, Daisuke Kitamura","doi":"10.1093/intimm/dxae047","DOIUrl":"https://doi.org/10.1093/intimm/dxae047","url":null,"abstract":"Glomerulonephritis (GN) is a group of heterogeneous immune-mediated kidney diseases that causes inflammation within the glomerulus. Autoantibodies (auto-Abs) are considered to be central effectors in the pathogenesis of several types of GN. IgA nephropathy (IgAN) is the most common GN worldwide and is characterized by deposition of IgA in the glomerular mesangium of the kidneys, which is thought to be mediated by immune complexes containing non-specific IgA. However, we recently reported that IgA auto-Abs specific to mesangial cells (anti-mesangium IgA) were found in the sera of gddY mice, a spontaneous IgAN model, and patients with IgAN. We identified two autoantigens (β2-spectrin and CBX3) that are selectively expressed on the mesangial cell surface and targeted by anti-mesangial IgA. Our findings redefined IgAN as a tissue-specific autoimmune disease. Regarding the mechanisms of production of anti-mesangium IgA, studies using gddY mice have revealed that production of anti-CBX3 IgA is induced by particular strains of commensal bacteria in the oral cavity, possibly through their molecular mimicry to CBX3. Here, we discuss a new concept of IgAN pathogenesis from the perspective of this disease as autoimmune GN caused by tissue-specific auto-Abs.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765984","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}

引用次数: 0

CCR2-dependent placental migration of inflammatory monocytes suppresses abnormal pregnancies caused by Toxoplasma gondii infection. 依赖 CCR2 的炎性单核细胞胎盘迁移可抑制弓形虫感染引起的异常妊娠。

IF 4.8 4区医学

International immunology Pub Date : 2024-07-25 DOI: 10.1093/intimm/dxae046

Naganori Kamiyama, Mai Ueno, Yuma Sasaki, Thanyakorn Chalalai, Nozomi Sachi, Sotaro Ozaka, Yasuhiro Soga, Yomei Kagoshima, Supanuch Ekronarongchai, Masaaki Okamoto, Masahiro Yamamoto, Takashi Kobayashi

{"title":"CCR2-dependent placental migration of inflammatory monocytes suppresses abnormal pregnancies caused by Toxoplasma gondii infection.","authors":"Naganori Kamiyama, Mai Ueno, Yuma Sasaki, Thanyakorn Chalalai, Nozomi Sachi, Sotaro Ozaka, Yasuhiro Soga, Yomei Kagoshima, Supanuch Ekronarongchai, Masaaki Okamoto, Masahiro Yamamoto, Takashi Kobayashi","doi":"10.1093/intimm/dxae046","DOIUrl":"https://doi.org/10.1093/intimm/dxae046","url":null,"abstract":"Toxoplasma gondii (T. gongii) is a zoonotic protozoan parasite that causes congenital toxoplasmosis, including fetal death, abortion, stillbirth, morphological abnormalities, and premature birth. Primary T. gondii infection in pregnant women results in congenital toxoplasmosis. C-C chemokine receptor (CCR) 2 is reportedly a critical host defense factor against T. gondii infection. However, details of the role of CCR2 in the host immune response to T. gondii in congenital toxoplasmosis remain unclear. Here, we infected pregnant CCR2-deficient mice with T. gondii, resulting in stillbirth, embryonic resorption, fetal morphological abnormalities, and preterm delivery at significantly higher rates than those in pregnant wild-type mice. Consistent with the severity of abnormal pregnancy, a large area of placental hemorrhage and a large number of T. gondii infections around the hemorrhagic area were observed in the placentas of CCR2-deficient mice. In addition, the accumulation of inflammatory monocytes in the placenta was reduced in CCR2-deficient mice during infection. We further confirmed that the adoptive transfer of inflammatory monocytes collected from wild-type mice into T. gondii-infected pregnant CCR2-deficient mice effectively suppressed placental damage and abnormal pregnancy. Collectively, CCR2 contributes to pregnancy maintenance by regulating the migration of inflammatory monocytes into the placenta of T. gondii-infected pregnant mice.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758568","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}

引用次数: 0

Identification of potential C1-binding sites in the immunoglobulin CL domains. 鉴定免疫球蛋白 CL 结构域中潜在的 C1 结合位点。

IF 4.8 4区医学

International immunology Pub Date : 2024-07-13 DOI: 10.1093/intimm/dxae017

Saeko Yanaka, Atsuji Kodama, Shigetaka Nishiguchi, Rina Fujita, Jiana Shen, Pornthip Boonsri, Duckyong Sung, Yukiko Isono, Hirokazu Yagi, Yohei Miyanoiri, Takayuki Uchihashi, Koichi Kato

{"title":"Identification of potential C1-binding sites in the immunoglobulin CL domains.","authors":"Saeko Yanaka, Atsuji Kodama, Shigetaka Nishiguchi, Rina Fujita, Jiana Shen, Pornthip Boonsri, Duckyong Sung, Yukiko Isono, Hirokazu Yagi, Yohei Miyanoiri, Takayuki Uchihashi, Koichi Kato","doi":"10.1093/intimm/dxae017","DOIUrl":"10.1093/intimm/dxae017","url":null,"abstract":"Immunoglobulin G (IgG) molecules that bind antigens on the membrane of target cells spontaneously form hexameric rings, thus recruiting C1 to initiate the complement pathway. However, our previous report indicated that a mouse IgG mutant lacking the Cγ1 domain activates the pathway independently of antigen presence through its monomeric interaction with C1q via the CL domain, as well as Fc. In this study, we investigated the potential interaction between C1q and human CL isoforms. Quantitative single-molecule observations using high-speed atomic force microscopy revealed that human Cκ exhibited comparable C1q binding capabilities with its mouse counterpart, surpassing the Cλ types, which have a higher isoelectric point than the Cκ domains. Nuclear magnetic resonance and mutation experiments indicated that the human and mouse Cκ domains share a common primary binding site for C1q, centred on Glu194, a residue conserved in the Cκ domains but absent in the Cλ domains. Additionally, the Cγ1 domain, with its high isoelectric point, can cause electrostatic repulsion to the C1q head and impede the C1q-interaction adjustability of the Cκ domain in Fab. The removal of the Cγ1 domain is considered to eliminate these factors and thus promote Cκ interaction with C1q with the potential risk of uncontrolled activation of the complement pathway in vivo in the absence of antigen. However, this research underscores the presence of potential subsites in Fab for C1q binding, offering promising targets for antibody engineering to refine therapeutic antibody design.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335484","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}

引用次数: 0

Immunogenicity and protective capacity of a CpG ODN adjuvanted alum adsorbed bivalent meningococcal outer membrane vesicle vaccine. CpG ODN 佐剂明矾吸附双价脑膜炎球菌外膜囊泡疫苗的免疫原性和保护能力

IF 4.8 4区医学

International immunology Pub Date : 2024-07-13 DOI: 10.1093/intimm/dxae016

Tugce Canavar Yildirim, Yasemin Ozsurekci, Muzaffer Yildirim, Irem Evcili, Volkan Yazar, Kubra Aykac, Ulku Guler, Bekir Salih, Mayda Gursel, Ihsan Gursel

{"title":"Immunogenicity and protective capacity of a CpG ODN adjuvanted alum adsorbed bivalent meningococcal outer membrane vesicle vaccine.","authors":"Tugce Canavar Yildirim, Yasemin Ozsurekci, Muzaffer Yildirim, Irem Evcili, Volkan Yazar, Kubra Aykac, Ulku Guler, Bekir Salih, Mayda Gursel, Ihsan Gursel","doi":"10.1093/intimm/dxae016","DOIUrl":"10.1093/intimm/dxae016","url":null,"abstract":"Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N. meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and the Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal activity (SBA) assay-based protective coverage of OMV vaccine to the X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the W + B OMV vaccine, either adjuvanted with Alum, CpG ODN, or their combinations, and compared with a MenACYW conjugate vaccine (NimenrixTM, Pfizer), and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through enzyme-linked immunosorbent assay (ELISA) and SBA assay. Antibody responses and SBA titers were significantly higher in the W + B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the W + B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the W + B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305534","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}

引用次数: 0

Recent advances regarding the potential roles of invariant natural killer T cells in cardiovascular diseases with immunological and inflammatory backgrounds. 关于不变自然杀伤 T 细胞在具有免疫和炎症背景的心血管疾病中的潜在作用的最新进展。

IF 4.8 4区医学

International immunology Pub Date : 2024-07-13 DOI: 10.1093/intimm/dxae019

Kazuya Iwabuchi, Masashi Satoh, Kazuhisa Yoshino, Naoki Ishimori

{"title":"Recent advances regarding the potential roles of invariant natural killer T cells in cardiovascular diseases with immunological and inflammatory backgrounds.","authors":"Kazuya Iwabuchi, Masashi Satoh, Kazuhisa Yoshino, Naoki Ishimori","doi":"10.1093/intimm/dxae019","DOIUrl":"10.1093/intimm/dxae019","url":null,"abstract":"Invariant natural killer T (iNKT) cells, which bear αβ-type T-cell antigen-receptors (TCRs), recognize glycolipid antigens in a cluster of differentiation 1d (CD1d)-restricted manner. Regarding these cells, the unique modes of thymic selection and maturation elucidate innateness, irrespective of them also being members of the adaptive immune system as a T-cell. iNKT cells develop and differentiate into NKT1 [interferon γ (IFN-γ)-producing], NKT2 [interleukin 4 (IL-4)/IL-13-producing], or NKT17 (IL-17-producing) subsets in the thymus. After egress, NKT10 (IL-10-producing), follicular helper NKT (NKTfh; IL-21-producing), and regulatory NKT (NKTreg) subsets emerge following stimulation in the periphery. Moreover, iNKT cells have been shown to possess several physiological or pathological roles. iNKT cells exhibit dual alleviating or aggravating roles in experimentally induced immune and/or inflammatory diseases in mice. These findings indicate that the modulation of iNKT cells can be employed for therapeutic use or prevention of human diseases. In this review, we discuss the potential roles of iNKT cells in the development of immune/inflammatory diseases of the cardiovascular system, with emphasis on atherosclerosis, aortic aneurysms, and cardiac remodeling.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335485","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}

引用次数: 0

Correction to: Computer model of IL-6-dependent rheumatoid arthritis in F759 mice. 更正：F759 小鼠 IL-6 依赖性类风湿性关节炎的计算机模型。

IF 4.8 4区医学

International immunology Pub Date : 2024-07-13 DOI: 10.1093/intimm/dxae030

引用次数: 0

The canonical Hippo pathway components modulate the differentiation of lamina propria regulatory T cells and T helper 17-like regulatory T cells in mouse colitis. 在小鼠结肠炎中，典型 Hippo 通路成分可调节固有膜调节性 T 细胞和 T 辅助 17 样调节性 T 细胞的分化。

IF 4.8 4区医学

International immunology Pub Date : 2024-07-03 DOI: 10.1093/intimm/dxae043

Liuqing Ge, Min Xu, Meifang Huang, Shaoping Liu, Zhidai Zhou, Ziqin Xia, Shouquan Dong, Qiu Zhao, Ruiping Zhu, Feng Zhou

{"title":"The canonical Hippo pathway components modulate the differentiation of lamina propria regulatory T cells and T helper 17-like regulatory T cells in mouse colitis.","authors":"Liuqing Ge, Min Xu, Meifang Huang, Shaoping Liu, Zhidai Zhou, Ziqin Xia, Shouquan Dong, Qiu Zhao, Ruiping Zhu, Feng Zhou","doi":"10.1093/intimm/dxae043","DOIUrl":"https://doi.org/10.1093/intimm/dxae043","url":null,"abstract":"Regulatory T cells (Tregs) ameliorate inflammatory bowel diseases. However, their plasticity is not completely understood. In this study using a mouse colitis model, Tregs and T helper 17 (Th17)-like Tregs were detected and sorted using flow cytometry, followed by transcriptome sequencing, real-time RT-PCR, and flow cytometry to analyze the mRNA profiles of these cells. Treg plasticity was evaluated by in vitro differentiation assays. The immunosuppressive activities of Tregs and Th17-like Tregs were assessed in an adoptive transfer assay. We found Tregs-derived Th17-like Tregs in inflamed colonic lamina propria (LP). LP Th17-like Tregs expressed higher Th17-related cytokines and lower immunosuppressive cytokines compared with LP Tregs. Notably, Tregs expressed higher Yes-associated protein 1 (YAP1) but lower transcriptional coactivator with PDZ‑binding motif (TAZ) than Th17-like Tregs. Verteporfin-mediated inhibition of YAP1 activity enhanced Th17-like Treg generation, whereas IBS008739-induced TAZ activation did not affect Th17-like Treg generation. Besides, verteporfin enhanced while IBS008739 suppressed the differentiation of Th17-like Tregs into Th17 cells. Furthermore, YAP1 activated STAT5 signaling in Tregs, whereas YAP1 and TAZ activated STAT3 and STAT5 signaling in Th17-like Tregs. Compared with Tregs, Th17-like Tregs were less efficacious in ameliorating colitis. Therefore, YAP1 suppressed Treg differentiation into Th17-like Tregs. Both YAP1 and TAZ inhibited the differentiation of Th17-like Tregs into Th17 cells. Therefore, YAP1 and TAZ probably maintain the immunosuppressive activities of Tregs and Th17-like Tregs in colitis.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491814","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}

引用次数: 0

Diverse roles of dendritic cell and regulatory T cell crosstalk in controlling health and disease. 树突状细胞和调节性 T 细胞串联在控制健康和疾病方面的多种作用。

IF 4.8 4区医学

International immunology Pub Date : 2024-07-02 DOI: 10.1093/intimm/dxae042

Sayuri Yamazaki

{"title":"Diverse roles of dendritic cell and regulatory T cell crosstalk in controlling health and disease.","authors":"Sayuri Yamazaki","doi":"10.1093/intimm/dxae042","DOIUrl":"https://doi.org/10.1093/intimm/dxae042","url":null,"abstract":"Dendritic cells (DCs) are specialized antigen-presenting cells for lymphocytes, including regulatory T (Treg) cells, a subset of CD4+ T cells expressing CD25 and Foxp3, a transcription factor. Treg cells maintain immunological self-tolerance in mice and humans, and suppress autoimmunity and other various immune responses such as tumor immunity, transplant rejection, allergy, responses to microbes, and inflammation. Treg cell proliferation is controlled by antigen-presenting DCs. On the other hand, Treg cells suppress the function of DCs by restraining DC maturation. Therefore, the interaction between DCs and Treg cells, DC-Treg crosstalk, could contribute to controlling health and disease. We recently found that unique DC-Treg crosstalk plays a role in several conditions. First, Treg cells are expanded in ultraviolet-B (UVB)-exposed skin by interacting with DCs, and the UVB-expanded Treg cells have a healing function. Second, manipulating DC-Treg crosstalk can induce effective acquired immune responses against SARS-CoV2 antigens without adjuvants. Third, Treg cells with a special feature interact with DCs in the tumor microenvironment of human head and neck squamous cell cancer, which may contribute to the prognosis. Understanding the underlying mechanisms of DC-Treg crosstalk may provide a novel strategy to control health and disease.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491813","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}

引用次数: 0

New approaches to the control of chronic inflammatory diseases with a focus on the endolysosomal system of immune cells. 控制慢性炎症性疾病的新方法，重点关注免疫细胞的内溶酶体系统。

IF 4.8 4区医学

International immunology Pub Date : 2024-07-01 DOI: 10.1093/intimm/dxae041

Noriko Toyama-Sorimachi

{"title":"New approaches to the control of chronic inflammatory diseases with a focus on the endolysosomal system of immune cells.","authors":"Noriko Toyama-Sorimachi","doi":"10.1093/intimm/dxae041","DOIUrl":"https://doi.org/10.1093/intimm/dxae041","url":null,"abstract":"Chronic inflammation is implicated in many types of diseases, including cardiovascular, neurodegenerative, metabolic, and immune disorders. The search for therapeutic targets to control chronic inflammation often involves narrowing down the various molecules associated with pathology that have been discovered by various omics analyses. Herein, a different approach to identify therapeutic targets against chronic inflammation is proposed and one such target is discussed as an example. In chronically inflamed tissues, a large number of cells receive diverse proinflammatory signals, the intracellular signals are intricately integrated, and complicated intercellular interactions are orchestrated. This review focuses on effectively blocking this chaotic inflammatory signaling network via the endolysosomal system, which acts as a cellular signaling hub. In endolysosomes, the inflammatory signals mediated by pathogen sensors, such as Toll-like receptors, and the signals from nutrient and metabolic pathways are integrally regulated. Disruption of endolysosome signaling results in a strong anti-inflammatory effect by disrupting various signaling pathways, including pathogen sensor-mediated signals, in multiple immune cells. The endolysosome-resident amino acid transporter, solute carrier family 15 member 4 (SLC15A4), which plays an important role in the regulation of endolysosome-mediated signals, is a promising therapeutic target for several inflammatory diseases, including autoimmune diseases. The mechanisms by which SLC15A4 regulates inflammatory responses may provide a proof of concept for the efficacy of therapeutic strategies targeting immune cell endolysosomes.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467800","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}

引用次数: 0