International immunology最新文献

The Arf pathway is required for resolving ER stress during T cell activation. 在T细胞活化过程中，Arf通路是解决内质网应激所必需的。

IF 4.8 4区医学

International immunology Pub Date : 2025-05-23 DOI: 10.1093/intimm/dxaf028

Mami Sumiyoshi, Yui Kotani, Chikako Shimokawa, Sukhonthip Khueangchiangkhwang, Yoichi Maekawa, Yoshiyuki Matsuo, Yoshiki Yasukochi, Koichiro Higasa, Yasunori Kanaho, Toshio Watanabe, Satoshi Matsuda

{"title":"The Arf pathway is required for resolving ER stress during T cell activation.","authors":"Mami Sumiyoshi, Yui Kotani, Chikako Shimokawa, Sukhonthip Khueangchiangkhwang, Yoichi Maekawa, Yoshiyuki Matsuo, Yoshiki Yasukochi, Koichiro Higasa, Yasunori Kanaho, Toshio Watanabe, Satoshi Matsuda","doi":"10.1093/intimm/dxaf028","DOIUrl":"https://doi.org/10.1093/intimm/dxaf028","url":null,"abstract":"Upon antigen recognition, T cells undergo rapid cell proliferation and differentiation, which is accompanied by a drastic change in cellular metabolism. The ADP-ribosylation factor (Arf) pathway contributes to cellular homeostasis by orchestrating vesicle trafficking, and our previous study using mice lacking both Arf1 and Arf6 (Arf-KO) revealed that Th17-mediated autoimmune diseases were markedly suppressed in Arf-KO mice though its precise mechanism remained elusive. Here, we show that Arf pathway modulates cellular metabolism in T cell activation and survival. We found that the lack of Arf1 and Arf6 resulted in hyper-activation of mTORC1, a master regulator of cellular metabolism, as well as unresolved endoplasmic reticulum (ER) stress, leading to exaggerated apoptosis during T cell activation. We further demonstrated that treatment with IL-21, a potent inducer of Tfh differentiation, rescued Arf-KO T cells from apoptosis by attenuating ER stress in vitro. Accordingly, antigen-specific antibody production and host defenses against infections such as Leishmania major or Heligmosomoides polygyrus infections were significantly preserved in Arf-KO mice. Taken together, these findings provide mechanistic insights linking the Arf pathway with T cells homeostasis during activation and identify the Arf pathway as an ideal therapeutic target for autoimmune diseases with a low risk of opportunistic infections.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127626","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

SLAMF6 regulates basal T cell receptor signaling and influences invariant natural killer T cell lineage diversity. SLAMF6调节基础T细胞受体信号传导并影响不变的自然杀伤T细胞谱系多样性。

IF 4.8 4区医学

International immunology Pub Date : 2025-05-23 DOI: 10.1093/intimm/dxaf030

Yukihiro Endo, Ichita Hasegawa, Akemi Igi, Atsushi Onodera, Satomi Mita, Koichi Higashi, Ken Kurokawa, Atsushi Toyoda, Masahiro Kiuchi, Miho Shinzawa, Yangsong Wang, Ryo Koyama-Nasu, Kiyoshi Hirahara, Shinichiro Motohashi, Toshinori Nakayama, Motoko Y Kimura

{"title":"SLAMF6 regulates basal T cell receptor signaling and influences invariant natural killer T cell lineage diversity.","authors":"Yukihiro Endo, Ichita Hasegawa, Akemi Igi, Atsushi Onodera, Satomi Mita, Koichi Higashi, Ken Kurokawa, Atsushi Toyoda, Masahiro Kiuchi, Miho Shinzawa, Yangsong Wang, Ryo Koyama-Nasu, Kiyoshi Hirahara, Shinichiro Motohashi, Toshinori Nakayama, Motoko Y Kimura","doi":"10.1093/intimm/dxaf030","DOIUrl":"https://doi.org/10.1093/intimm/dxaf030","url":null,"abstract":"Invariant natural killer T (iNKT) cells differentiate into at least three distinct subsets within the thymus, with each subset's frequency varying considerably among mouse strains; however, the molecular mechanisms involved remain unclear. We herein report that iNKT cell lineage diversity results from the significant expansion of iNKT2 cells with limited T cell receptor (TCR) diversity in BALB/c mice and the selection of iNKT1 cells with significantly diverse TCRs in B6 mice. Furthermore, SLAMF6 expression on immature thymocytes significantly differs among mouse strains, with the low expression of SLAMF6 on BALB/c immature thymocytes resulting in high \"basal TCR signaling\" in preselected DP thymocytes, associated with iNKT cell expansion. Our data suggest that the expression level of SLAMF6 on immature thymocytes affects basal TCR signaling in preselected DP thymocytes, which may influence thymocyte development in a T-cell subset.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127622","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

The impact of Talin2, a signaling protein regulating the focal adhesion complex, on asthma. Talin2（一种调节局灶黏附复合物的信号蛋白）对哮喘的影响。

IF 4.8 4区医学

International immunology Pub Date : 2025-05-22 DOI: 10.1093/intimm/dxaf026

Da Yeon Hwang, Min-Hyeok An, Pureun-Haneul Lee, Sang Min Yoon, Yunha Nam, Shinhee Park, Ae-Rin Baek, An-Soo Jang

{"title":"The impact of Talin2, a signaling protein regulating the focal adhesion complex, on asthma.","authors":"Da Yeon Hwang, Min-Hyeok An, Pureun-Haneul Lee, Sang Min Yoon, Yunha Nam, Shinhee Park, Ae-Rin Baek, An-Soo Jang","doi":"10.1093/intimm/dxaf026","DOIUrl":"https://doi.org/10.1093/intimm/dxaf026","url":null,"abstract":"Talin protein as a mechanosensitive cytoskeleton protein connect the extracellular matrix to the cytoskeleton by linking to integrins and actin, thereby mediating the conversion of mechanical signals into biochemical signals and influencing disease progression. The biological significance of Talin2 in asthma is not well understood. The aim of this study was to elucidate the role of Talin2 in asthma. Mice sensitized and challenged with ovalbumin (OVA) or saline and MRC-5 cells were used to investigate the role of Talin2 in the pathogenesis of bronchial asthma. In addition, Talin2 levels were measured in the plasma of control subjects and asthmatic patients. The relationships between Talin2 and clinical variables in asthmatic patients were also examined. Plasma Talin2 levels were higher in asthmatic patients than control subjects. In asthmatic patients, Talin2 levels correlated with FEV1 % pred., FVC % pred., and FEV1/FVC, and the blood neutrophils and lymphocyte proportion. The ROC curves for Talin2 levels differed between control subjects and asthmatic patients. Talin2, Kindlin2, Integrin β1 and F-actin levels were significantly increased in MRC-5 cells exposed to Der p 1, but decreased in MRC-5 cells treated with talin2 siRNA. The BALF and serum levels of cytokines (IL-4, IL-5, and TNF-α) were elevated in OVA mice compared to the control mice. Talin2, Kindlin2, Integrin β1, and F-actin protein expression in lung tissue was significantly higher in OVA mice than control mice. These results suggest that Talin2 be involved in the pathogenesis of asthma, and may be a marker for asthma.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119681","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

Beneficial effects on T cells by photodynamic therapy with talaporfin enhance cancer immunotherapy. talaporfin光动力治疗对T细胞的有益作用增强了癌症免疫治疗。

IF 4.8 4区医学

International immunology Pub Date : 2025-05-21 DOI: 10.1093/intimm/dxaf003

Ehab M Ezzaldeen, Tomonori Yaguchi, Ryotaro Imagawa, Mohamed A Soltan, Akira Hirata, Kosaku Murakami, Hirotake Tsukamoto, Manabu Muto, Tasuku Honjo, Kenji Chamoto

{"title":"Beneficial effects on T cells by photodynamic therapy with talaporfin enhance cancer immunotherapy.","authors":"Ehab M Ezzaldeen, Tomonori Yaguchi, Ryotaro Imagawa, Mohamed A Soltan, Akira Hirata, Kosaku Murakami, Hirotake Tsukamoto, Manabu Muto, Tasuku Honjo, Kenji Chamoto","doi":"10.1093/intimm/dxaf003","DOIUrl":"10.1093/intimm/dxaf003","url":null,"abstract":"Photodynamic therapy (PDT), a local cancer treatment using photosensitizers, has been reported to enhance antitumor immune responses by inducing immunogenic cell death. Although several studies have demonstrated the synergistic antitumor effects of PDT and immune checkpoint blockage (ICB), the detailed underlying mechanisms remain poorly understood. In this study, we investigated the immunological effects of PDT with talaporfin (Tal-PDT), a clinically approved photosensitizer, using bilateral tumor-bearing mouse models. Treatment with Tal-PDT on the tumor on one side of the mouse resulted in tumor growth inhibition on the untreated opposite side. This phenomenon, accompanied by tumor antigen-specific immune reactions, is indicative of an abscopal effect. When combined with anti PD-L1 antibody, synergistic antitumor effects were observed on both the laser-treated and untreated sides. Mechanistically, Tal-PDT enhanced the induction of XCR-1+ dendritic cells in the proximal draining lymph node likely through the induction of ferroptosis in tumor cells. This, in turn, led to the systemic generation of precursor-exhausted CD8+ T cells. Moreover, talaporfin was selectively incorporated into tumor cells rather than into tumor-infiltrating T cells in vivo, leading to targeted tumor killing while preserving T cells. These beneficial effects of Tal-PDT on antitumor immunity collectively enhance ICB cancer immunotherapy. Our study demonstrates the potential of combining Tal-PDT with ICB therapy for clinical applications.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"313-324"},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023421","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

CD20 and CD19 promote proliferation driven by the IgM-TLR9-L265P MyD88 complex. CD20和CD19促进IgM-TLR9-L265P MyD88复合体驱动的增殖。

IF 4.8 4区医学

International immunology Pub Date : 2025-05-21 DOI: 10.1093/intimm/dxaf004

Yohei Kobayashi, Ryota Sato, Yuri Shimizu, Ryutaro Fukui, Takuma Shibata, Hiroki Tsukamoto, Takeshi Tsubata, Kensuke Miyake

{"title":"CD20 and CD19 promote proliferation driven by the IgM-TLR9-L265P MyD88 complex.","authors":"Yohei Kobayashi, Ryota Sato, Yuri Shimizu, Ryutaro Fukui, Takuma Shibata, Hiroki Tsukamoto, Takeshi Tsubata, Kensuke Miyake","doi":"10.1093/intimm/dxaf004","DOIUrl":"10.1093/intimm/dxaf004","url":null,"abstract":"The cancer driver mutation L265P MyD88 is found in approximately 30% of cases in the activated B cell-like subgroup of diffuse large B cell-like lymphoma (ABC DLBCL). L265P MyD88 forms a complex with TLR9 and IgM, referred to as the My-T-BCR complex, to drive proliferation. We here show that the B cell surface molecules CD19 and CD20 enhance proliferation mediated by the My-T-BCR complex. Using the interleukin 3 (IL-3)-dependent Ba/F3 line transduced to express the IgM complex (IgM, CD79a, and CD79b) and TLR9, we observed proliferation in the presence of anti-IgM antibody and the TLR9 ligand CpG-B. TLR9 was constitutively associated with IgM and L252P MyD88. CD19 promoted proliferation with anti-IgM and CpG-B specifically in L252P MyD88-expressing Ba/F3 cells, while CD20 enhanced the proliferation in both wild-type- and L252P MyD88-expressing Ba/F3 cells. Additionally, CD20 uniquely enabled IgM-mediated proliferation in L252P MyD88-expressing Ba/F3 cells. Although CpG-B was not required for this proliferation, TLR9 expression remained indispensable. In the ABC DLBCL line TMD8, anti-IgM antibody-mediated growth was impaired by the lack of CD20 and CD19 or of TLR9. Mechanistically, CD19 promoted IgM-dependent AKT phosphorylation, whereas CD20 increased expression of cell surface IgM, thereby enhancing the formation of the IgM-TLR9 complex. These findings suggest that CD19 and CD20 differentially contribute to the proliferation driven by the My-T-BCR complex.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"325-337"},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046621","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

TLR7 responses in glomerular macrophages accelerate the progression of glomerulonephritis in NZBWF1 mice. TLR7在肾小球巨噬细胞中的应答加速了NZBWF1小鼠肾小球肾炎的进展。

IF 4.8 4区医学

International immunology Pub Date : 2025-05-21 Epub Date: 2025-01-27 DOI: 10.1093/intimm/dxaf005

Reika Tanaka, Yusuke Murakami, Dorothy Ellis, Jun Seita, Wu Yinga, Shigeru Kakuta, Keiki Kumano, Ryutaro Fukui, Kensuke Miyake

{"title":"TLR7 responses in glomerular macrophages accelerate the progression of glomerulonephritis in NZBWF1 mice.","authors":"Reika Tanaka, Yusuke Murakami, Dorothy Ellis, Jun Seita, Wu Yinga, Shigeru Kakuta, Keiki Kumano, Ryutaro Fukui, Kensuke Miyake","doi":"10.1093/intimm/dxaf005","DOIUrl":"10.1093/intimm/dxaf005","url":null,"abstract":"Systemic lupus erythematosus is a systemic autoimmune disease characterized by the production of autoantibodies and damage to multiple organs. Glomerulonephritis, a manifestation involving glomerular deposition of immune complexes and complement components, significantly contributes to disease morbidity. Although an endosomal single-stranded RNA sensor [Toll-like receptor 7 (TLR7)] is known to drive glomerulonephritis by promoting autoantibody production in B cells, the contribution of macrophage TLR7 responses to glomerulonephritis remains poorly understood. Here, we have examined Tlr7‒/‒ NZBWF1 (New Zealand Black/New Zealand White F1) mice and found that TLR7 deficiency ameliorates lupus nephritis by abolishing autoantibody production against RNA-associated antigens, C3 deposition, and macrophage accumulation in glomeruli. Furthermore, TLR7 signaling increased CD31 expression on glomerular endothelial cells and Ly6Clow macrophages but not on T and B cells, suggesting that CD31 mediates TLR7-dependent migration of monocytes into glomeruli. Compared to their splenic counterparts, glomerular macrophages produced IL-1β in a TLR7-dependent manner. In addition, single-cell RNA sequencing of glomerular macrophages revealed that TLR7 signaling induced expression of lupus-associated genes, including those encoding Chitinase 3 like 1, ferritin heavy chain 1, IKKε, and complement factor B (CfB). Although serum CfB did not increase in NZBWF1 mice, TLR7-dependent CfB protein expression was detected in glomerular macrophages. In addition, TLR7 signaling promoted C3 cleavage and deposition predominantly on mesangial cells. These findings suggest that TLR7 responses in glomerular macrophages accelerate the progression of glomerulonephritis in NZBWF1 mice.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":"37 6","pages":"339-353"},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119682","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

The TET-TDG axis in T cells and biological processes. T细胞和生物过程中的TET-TDG轴。

IF 4.8 4区医学

International immunology Pub Date : 2025-05-21 DOI: 10.1093/intimm/dxaf006

Kazumasa Suzuki, Anjana Rao, Atsushi Onodera

{"title":"The TET-TDG axis in T cells and biological processes.","authors":"Kazumasa Suzuki, Anjana Rao, Atsushi Onodera","doi":"10.1093/intimm/dxaf006","DOIUrl":"10.1093/intimm/dxaf006","url":null,"abstract":"Ten-eleven translocation (TET) proteins are dioxygenases that sequentially oxidize the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). All three epigenetic modifications are intermediates in DNA demethylation. In the \"passive\" (replication-dependent) DNA demethylation pathway, sequential oxidation reactions by TETs are essential and modified cytosines (C) are diluted at each cycle of DNA replication. In the \"active\" (replication-independent) DNA demethylation pathway, both thymine DNA glycosylase (TDG) and TETs play important roles. TDG removes 5fC and 5caC from 5fC:G and 5caC:G base pairs and these modified bases are replaced by unmodified C via base excision repair. Through epigenetic regulation of DNA demethylation, TETs and TDG are involved in cell development, differentiation, and homeostasis. The interplay between TDG and TETs is involved in embryo development, stem cell differentiation, neural development, immune responses, and tumorigenesis. Loss-of-function mutations of TET proteins in immune cells are associated with a variety of abnormalities, including inflammation, cancer, and clonal hematopoiesis, a condition related to aging. Loss of TETs also has a significant impact on the plasticity and differentiation of T cells, which contributes to inflammation and cancer. In this review, we describe recent findings in functions of TETs in T cell plasticity and differentiation and the TET-TDG axis in selected biological processes.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"299-312"},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373958","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

Correlation of interferons and autoimmune aspects in long COVID-19 patients. 长期COVID-19患者干扰素与自身免疫方面的相关性

IF 4.8 4区医学

International immunology Pub Date : 2025-05-21 DOI: 10.1093/intimm/dxaf008

Fumiyuki Hattori, Junji Nishiyama, Hideaki Hasuo

{"title":"Correlation of interferons and autoimmune aspects in long COVID-19 patients.","authors":"Fumiyuki Hattori, Junji Nishiyama, Hideaki Hasuo","doi":"10.1093/intimm/dxaf008","DOIUrl":"10.1093/intimm/dxaf008","url":null,"abstract":"Long COVID, or post-acute sequelae of COVID-19 (PASC), represents a major global health challenge, with its underlying mechanisms remaining poorly understood despite substantial research and clinical trials. This study investigates the role of the interferon (IFN) axis in the pathogenesis of PASC, drawing parallels to systemic lupus erythematosus (SLE). The potential pathogenic role of IFNs was detected by meta-analyses of mRNA sequencing data comparing PASC patients to healthy controls. We analyzed serum samples from 39 PASC patients and found significant correlations among multiple IFN sub types, including IFN alpha-2, beta, gamma, lambda-1, and lambda-2/3. The biological activity of IFNs in the serum was positively correlated with levels of both total and type III IFNs. Notably, we detected the widespread presence of anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies in these patients, with anti-dsDNA levels showing a strong correlation with IFN activity. On the basis of these findings, we propose a hypothetical autoimmune pathogenesis for PASC highlighting the crucial role of IFN signaling.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"355-363"},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373956","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

Secreted phospholipase A2 regulates intercellular communications by coordinating extracellular phospholipid metabolism. 分泌磷脂酶A2通过协调细胞外磷脂代谢调节细胞间通讯。

IF 4.8 4区医学

International immunology Pub Date : 2025-05-20 DOI: 10.1093/intimm/dxaf027

Makoto Murakami

{"title":"Secreted phospholipase A2 regulates intercellular communications by coordinating extracellular phospholipid metabolism.","authors":"Makoto Murakami","doi":"10.1093/intimm/dxaf027","DOIUrl":"https://doi.org/10.1093/intimm/dxaf027","url":null,"abstract":"Lipids play fundamental roles in life. In essence, \"phospholipase A2\" (PLA2) indicates a group of enzymes that release fatty acids and lysophospholipids by hydrolyzing the sn-2 position of glycerophospholipids. To date, more than 50 enzymes that possess PLA2 or related lipid-metabolizing activities have been identified in mammals and are subdivided into several families in terms of their structures, catalytic mechanisms, tissue/cellular localizations, and evolutionary relationships. Among the PLA2 superfamily, the secreted PLA2 (sPLA2) family contains 11 isoforms in mammals, each of which has unique substrate specificity and tissue/cellular distributions. Recent studies using gene-manipulated (knockout and/or transgenic) mice for a full set of sPLA2s have revealed their diverse roles in immunity, metabolism, and other biological events. Application of mass spectrometric lipidomics to these mice has allowed the identification of target substrates and products of individual sPLA2s in tissue microenvironments. In principle, sPLA2s hydrolyze extracellular phospholipids such as those in extracellular vesicles, microbes, lipoproteins, surfactants, and ingested foods, as well as phospholipids in the plasma membrane of activated or damaged cells, thereby exacerbating or ameliorating various diseases. The actions of sPLA2s are dependent on, or independent of, the generation of free fatty acids, lysophospholipids, or their metabolites (lipid mediators) according to pathophysiological contexts. In this review, I will make an overview of recent understanding of the unexplored immunoregulatory roles of sPLA2s and their underlying lipid pathways, especially focusing on their unique actions on extracellular vesicles, activated/damaged cells, and gut microbiota.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110078","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

Central compartment of nasal cavity-derived MMP-9 enhances mixed-type 2 inflammation in eosinophilic chronic rhinosinusitis. 鼻腔中央隔室来源的MMP-9增强嗜酸性慢性鼻窦炎的混合2型炎症。

IF 4.8 4区医学

International immunology Pub Date : 2025-05-07 DOI: 10.1093/intimm/dxaf025

Takeshi Tsuda, Soichiro Fujii, Sho Obata, Kazuya Takeda, Masaki Hayama, Yohei Maeda, Ayaka Nakatani, Naoki Umeda, Miyu Saito, Kentaro Fujii, Toshihiro Kishikawa, Hidenori Tanaka, Kiyohito Hosokawa, Takashi Sato, Yukinori Takenaka, Daisuke Okuzaki, Satoshi Nojima, Masaru Ishii, Hidenori Inohara

{"title":"Central compartment of nasal cavity-derived MMP-9 enhances mixed-type 2 inflammation in eosinophilic chronic rhinosinusitis.","authors":"Takeshi Tsuda, Soichiro Fujii, Sho Obata, Kazuya Takeda, Masaki Hayama, Yohei Maeda, Ayaka Nakatani, Naoki Umeda, Miyu Saito, Kentaro Fujii, Toshihiro Kishikawa, Hidenori Tanaka, Kiyohito Hosokawa, Takashi Sato, Yukinori Takenaka, Daisuke Okuzaki, Satoshi Nojima, Masaru Ishii, Hidenori Inohara","doi":"10.1093/intimm/dxaf025","DOIUrl":"https://doi.org/10.1093/intimm/dxaf025","url":null,"abstract":"Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper respiratory tract. Although previously classified based on the presence or absence of nasal polyps, it is now commonly classified by endotype. Eosinophilic CRS (ECRS) is based on type 2 inflammation and the formation of intractable nasal polyps with eosinophil infiltration. Endoscopic surgery is the preferred treatment modality; however, recurrent cases are common. The central compartment of the nasal cavity has been implicated in these recurrences. Notably, the middle turbinate is considered crucial, but discussions have primarily focused on its anatomical significance. To date, there lacks a biochemical perspective on the role of the middle turbinate in recurrence. In this study, we evaluated the role of the middle turbinate as a source of inflammation in ECRS. Differences in gene expression between ECRS and non-ECRS (NECRS) middle turbinates were evaluated using RNA sequencing. Gene changes induced by MMP-9 stimulation of human nasal epithelial cells were also evaluated by RNA sequencing. Comprehensive analysis showed an enhanced IL-4 signaling pathway in the ECRS middle turbinate. Additionally, gene expression of matrix metalloproteinase-9 (MMP-9) was higher in the middle turbinates of patients with ECRS than in those with NECRS (P=0.002). Furthermore, MMP-9 has been found to act on human nasal epithelial cells to enhance pathways such as IL-17, IL-6, and S100 family signaling. MMP-9 in the central compartment of the nasal cavity exacerbates ECRS by induction mixed-type 2 inflammation and airway remodeling.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984520","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