Journal of immunology最新文献_第4页

Scopolamine ameliorates psoriasis by blocking M1 receptor-mediated IL-23 production in dendritic cells. 东莨菪碱通过阻断M1受体介导的树突状细胞中IL-23的产生来改善银屑病。

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag179

Yue Wu, Ziyang Zhang, Xiaojie Cai, Yang Sun, Fangzhou Lou, Zhikai Wang, Yan Li, Xichen Zheng, Xiuli Yang, Wenxiang Ding, Zilong Fang, Jing Zou, Zhenyao Xu, Siyu Deng, Aie Xu, Buwei Yu, Qifang Li, Honglin Wang

{"title":"Scopolamine ameliorates psoriasis by blocking M1 receptor-mediated IL-23 production in dendritic cells.","authors":"Yue Wu, Ziyang Zhang, Xiaojie Cai, Yang Sun, Fangzhou Lou, Zhikai Wang, Yan Li, Xichen Zheng, Xiuli Yang, Wenxiang Ding, Zilong Fang, Jing Zou, Zhenyao Xu, Siyu Deng, Aie Xu, Buwei Yu, Qifang Li, Honglin Wang","doi":"10.1093/jimmun/vkag179","DOIUrl":"https://doi.org/10.1093/jimmun/vkag179","url":null,"abstract":"Psoriasis is a chronic inflammatory skin disease involving intricate neuroimmune crosstalk. However, the specific mechanisms and therapeutic targets remain elusive. In this study, a pilot clinical trial demonstrated that intravenous scopolamine, a muscarinic receptor antagonist, significantly ameliorated skin lesions in psoriasis patients. Consistently, scopolamine reduced inflammation in an imiquimod-induced mouse model. Metabolomic profiling identified acetylcholine (ACh) as a significantly upregulated neurotransmitter in psoriatic skin, and exogenous ACh exacerbated inflammatory phenotypes. To pinpoint the cellular target, single-cell RNA sequencing revealed that dendritic cells (DCs), unlike T cells or macrophages, uniquely coexpressed neurointeraction receptors and the pathogenic cytokine Il23a. Mechanistically, scopolamine competitively inhibited ACh binding to M1 muscarinic receptors (M1Rs) on DCs, suppressing interleukin (IL)-23 secretion. This therapeutic efficacy was recapitulated in mice with DC-specific M1R deletion. Crucially, the protective effect of M1R deficiency was abolished by recombinant IL-23 administration, whereas scopolamine failed to inhibit inflammation induced by direct IL-23 injection, confirming its action upstream of cytokine release. Collectively, our findings provide compelling evidence that scopolamine treats psoriasis by antagonizing elevated ACh and blocking M1 receptor-mediated IL-23 release in DCs.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Estrogen receptor beta limits T cell-mediated inflammation to maintain immune homeostasis. 雌激素受体β限制T细胞介导的炎症以维持免疫稳态。

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag238

Alyssia V Broncano, Sarah K McNeer, Sarah M Stark, Alicia Santin, Caroline M Schlessman, Michelle L Raymond, William B Tran, Nathan P Hall, Adrian D Kocinski, Nicholas P Ziats, Wendy A Goodman

{"title":"Estrogen receptor beta limits T cell-mediated inflammation to maintain immune homeostasis.","authors":"Alyssia V Broncano, Sarah K McNeer, Sarah M Stark, Alicia Santin, Caroline M Schlessman, Michelle L Raymond, William B Tran, Nathan P Hall, Adrian D Kocinski, Nicholas P Ziats, Wendy A Goodman","doi":"10.1093/jimmun/vkag238","DOIUrl":"10.1093/jimmun/vkag238","url":null,"abstract":"Many autoimmune diseases exhibit a female sex bias in prevalence and severity, yet the mechanisms for this remain unclear. 17β-estradiol (E2) is a steroid sex hormone with established immunomodulatory roles in CD4+ T cells, which express the nuclear estrogen receptors ERα and ERβ. Autoimmune disease patients exhibit reductions in ERβ expression, suggesting that dysregulated E2 signaling contributes to inflammation. We previously identified a novel role for ERβ in promoting the TGF-β-dependent differentiation of Foxp3+ Tregs, supporting the idea that ERβ has anti-inflammatory functions. In this study, we investigated the functional role of ERβ in effector T cells, which drive pathogenesis of many autoimmune diseases. CD4+ T cells isolated from mice globally deficient in ERβ (ERβ-KO) showed enhanced proliferation and polarization to Th1 and Th17 populations ex vivo and conferred more severe inflammation and experimental colitis when transferred to immunodeficient Rag-KO mice. Treatment of ERβ-KO T cells ex vivo with anti-CD3/28 and PMA/ionomycin resulted in robust activation-induced production of Th17-associated cytokines, suggesting that ERβ normally functions to restrain Th17. Collectively, our data support a model in which reduced ERβ expression may contribute to loss of immunoregulatory signaling and enhanced T cell-driven inflammation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Selenium serves as an immunomodulator adjunct to enhance the efficacy of anti-PD-1 therapy in non-small cell lung cancer. 硒作为一种免疫调节佐剂，可增强抗pd -1治疗非小细胞肺癌的疗效。

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag241

Kaiyuan Guo, Hongwei Hu, Naichen Yao, Qitai Zhao, Shasha Liu, Peng Wu, Yachang Huo, Pingchuan Ma, Tianran Chen, Xinfeng Chen, Guohui Qin, Yi Zhang

{"title":"Selenium serves as an immunomodulator adjunct to enhance the efficacy of anti-PD-1 therapy in non-small cell lung cancer.","authors":"Kaiyuan Guo, Hongwei Hu, Naichen Yao, Qitai Zhao, Shasha Liu, Peng Wu, Yachang Huo, Pingchuan Ma, Tianran Chen, Xinfeng Chen, Guohui Qin, Yi Zhang","doi":"10.1093/jimmun/vkag241","DOIUrl":"https://doi.org/10.1093/jimmun/vkag241","url":null,"abstract":"The role of selenium in tumor progression remains controversial, and its mechanisms of action in the context of immunotherapy are poorly understood. In this study, our findings indicate that selenium supplementation did not alter immune parameters, induce organ damage under healthy conditions, or affect the growth of Lewis lung cancer cells in vitro. In tumor-bearing mice, although selenium supplementation alone significantly enhanced the infiltration of CD8+ T cells into tumors, it failed to arrest tumor growth. Further analyses revealed that selenium treatment upregulated the expression of PD-1 on CD8+ T cells and PD-L1 on tumor cells. This finding suggests that PD-1/PD-L1 engagement may impair CD8+ T cell function, thereby preventing the effective elimination of tumor cells. Consequently, selenium supplementation exhibited a strong synergistic effect when combined with anti-PD-1 therapy, yielding enhanced antitumor responses. Single-cell RNA sequencing analysis revealed that the CD8-Prf1 subpopulation expanded and displayed enhanced proliferative and cytotoxic gene signatures after treatment with a combination of selenium and anti-PD-1. Clinically, a high abundance of this subpopulation was associated with prolonged survival in patients receiving anti-PD-1 treatment. Our results indicate that selenium is a promising immunomodulator adjunct that augments CD8+ T cell function and improves the response to anti-PD-1 therapy, supporting further clinical investigation of selenium supplementation in combination with immune checkpoint inhibitors for cancer treatment.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leishmania inhibits NLRP3 expression through IL-33/ST2 signaling driven SOCS1-mediated p65 degradation. 利什曼原虫通过IL-33/ST2信号驱动socs1介导的p65降解抑制NLRP3表达。

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag246

Souravi Roy, Mayumi Mandal, Madhurima Banerjee, Pratibha Madbhagat, Ajit Chande, Anindita Ukil

{"title":"Leishmania inhibits NLRP3 expression through IL-33/ST2 signaling driven SOCS1-mediated p65 degradation.","authors":"Souravi Roy, Mayumi Mandal, Madhurima Banerjee, Pratibha Madbhagat, Ajit Chande, Anindita Ukil","doi":"10.1093/jimmun/vkag246","DOIUrl":"https://doi.org/10.1093/jimmun/vkag246","url":null,"abstract":"The dynamic interplay between pro- and anti-inflammatory cytokines plays a crucial role in regulating host immune responses. In our earlier study, we showed that Leishmania donovani-induced IL-33 destabilizes host cytokine dynamics by downregulating TNF-α and IL-12 and ensures intramacrophage parasite survival. Another pertinent host favorable proinflammatory cytokine is Il-1β, maturation of which depends on the activation of NLRP3 inflammasome complex. Our present study highlights that independent neutralization of IL-33 and its receptor ST2, resulted in elevated levels of NLRP3 both at messenger RNA and protein levels, along with increased levels of mature IL-1β. Reduced NLRP3 expression during infection was correlated with decreased protein levels of p65, the major subunit of NF-κB transcription factor complex. An unaltered transcript level of p65 in infected macrophages along with reduced protein expression suggested that post-translational modification and ubiquitination-mediated p65 degradation in the presence of IL-33 was found to be driven by the ubiquitin ligase SOCS1. Administration of IL-33-neutralizing antibody in infected mice resulted in enhanced expression of both p65 and NLRP3, along with increased production of TNF-α, IL-12, and IL-1β, suggesting that IL-33 regulates these cytokines through a shared intermediary, p65. Neutralizing IL-33 during infection led to a reduction in SOCS1 expression, and SOCS1 knockdown by targeted short hairpin RNA in infected mice restores p65 levels, reactivates NLRP3 expressions, and reduces parasite burden in the visceral organs. This study highlights the IL-33/SOCS1 pathway as a potential target for host-directed therapeutic strategies aimed at restoring protective immunity during chronic leishmaniasis.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prostaglandin D2 production in obese mice is associated with reduced lung inflammation and improved control of Francisella tularensis and Bordetella pertussis infection. 肥胖小鼠前列腺素D2的产生与减少肺部炎症和改善土拉弗朗西斯菌和百日咳博德特菌感染的控制有关。

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag254

Monica A Valtierra-Alvarado, Lydia M Roberts, Forrest Jessop, Tara D Wehrly, Stacey M Thomas, Benjamin Schwarz, Eric Bohrnsen, Jeffrey Hablewitz, Greg Saturday, Carl Shaia, Catharine M Bosio

{"title":"Prostaglandin D2 production in obese mice is associated with reduced lung inflammation and improved control of Francisella tularensis and Bordetella pertussis infection.","authors":"Monica A Valtierra-Alvarado, Lydia M Roberts, Forrest Jessop, Tara D Wehrly, Stacey M Thomas, Benjamin Schwarz, Eric Bohrnsen, Jeffrey Hablewitz, Greg Saturday, Carl Shaia, Catharine M Bosio","doi":"10.1093/jimmun/vkag254","DOIUrl":"https://doi.org/10.1093/jimmun/vkag254","url":null,"abstract":"Obesity is a risk factor for severe respiratory viral infections, but its impact on bacterial respiratory diseases remains unclear and is sometimes paradoxical. Herein, we demonstrate that diet-induced obese, male C57BL/6J mice exhibited increased resistance to pulmonary infection with Francisella tularensis and Bordetella pertussis compared with lean controls. This enhanced protection in obese mice was associated with early production of the lipid mediator prostaglandin D2 (PGD2), reduced prostaglandin E2 levels, attenuated pulmonary inflammation and decreased lung cell death. Using in vitro models, we found that PGD2 and its metabolites, PGJ2 and 15-deoxy-PGJ2, suppressed macrophage inflammatory responses and limited replication of both F. tularensis and B. pertussis. In studies using the highly virulent F. tularensis SchuS4 strain, antagonism of the PGD2 receptor DP2 increased bacterial burden in macrophages in vitro, and activation of both PGD2 receptors (DP1 and DP2) in lean mice reduced bacterial loads and lung inflammation in vivo. Together, these data indicate that PGD2 signaling promotes bacterial control and limits inflammation during these bacterial infections. The association between early PGD2 production and enhanced resistance to F. tularensis and B. pertussis in obese mice suggests that modulation of PGD2 signaling may contribute to obesity-associated protection and represents a potential host-directed therapeutic strategy to improve protection of these infections.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Metabolic adaptations of inflammatory macrophages govern ferroptosis susceptibility via the GCH1-BH4-iNOS axis. 更正：炎性巨噬细胞的代谢适应通过GCH1-BH4-iNOS轴调控铁死亡易感性。

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag239

引用次数: 0

Mechanism of SGLT2 inhibitors in improving immune imbalance in diabetic mice with sepsis via regulating macrophage M2 polarization through the APOC1/HMGB1/TLR4 axis. SGLT2抑制剂通过APOC1/HMGB1/TLR4轴调节巨噬细胞M2极化改善糖尿病脓毒症小鼠免疫失衡的机制

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag240

TingTing You, HuoBao Yang, Gang Chen

{"title":"Mechanism of SGLT2 inhibitors in improving immune imbalance in diabetic mice with sepsis via regulating macrophage M2 polarization through the APOC1/HMGB1/TLR4 axis.","authors":"TingTing You, HuoBao Yang, Gang Chen","doi":"10.1093/jimmun/vkag240","DOIUrl":"https://doi.org/10.1093/jimmun/vkag240","url":null,"abstract":"This study aimed to investigate the mechanism by which the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin improves immune imbalance in sepsis with diabetes, focusing on its regulation of macrophage M2 polarization through the APOC1/HMGB1/TLR4 axis. A mouse model of type 2 diabetes was established through intraperitoneal injection of streptozotocin, after which sepsis was induced by cecal ligation and puncture. For in vitro studies, RAW264.7 macrophages and bone marrow-derived macrophages were exposed to high glucose and lipopolysaccharide. Molecular docking was employed to examine potential binding between dapagliflozin and APOC1. Organ pathology in lung, liver, and kidney was evaluated using hematoxylin and eosin staining and biochemical assay kits. Expression levels of APOC1, HMGB1, TLR4, and macrophage M1/M2 markers were analyzed via immunohistochemistry and immunofluorescence. Inflammatory cytokine levels were quantified with enzyme-linked immunosorbent assay. The SGLT2 inhibitor dapagliflozin effectively alleviated lung, liver, kidney injury and dysfunction and reduced inflammatory responses in diabetic mice with sepsis. The treatment also decreased inflammatory cytokine levels in the high glucose/lipopolysaccharide-stimulated cellular model. Furthermore, dapagliflozin treatment significantly increased the levels of M2 macrophage markers in both in vivo and in vitro models. Mechanistically, dapagliflozin was found to target, bind to, and downregulate APOC1 expression. Further investigations revealed that APOC1 promotes macrophage M1 polarization via the APOC1/HMGB1/TLR4 axis, an effect reversed by dapagliflozin. The SGLT2 inhibitor dapagliflozin ameliorates organ damage and inflammation in sepsis with diabetes by promoting macrophage M2 polarization through inhibition of the APOC1/HMGB1/TLR4 axis.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-mobility group N proteins are required for regulation of antigen-presentation genes in macrophages. 巨噬细胞中抗原呈递基因的调控需要高迁移率的N组蛋白。

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag256

Kyu-Seon Oh, Mahamat Babagana, Sayantan Chakraborty, Mohammad Aqdas, Alicja Pacholewska, Daisy Dahiya, Michael Bustin, Myong-Hee Sung

{"title":"High-mobility group N proteins are required for regulation of antigen-presentation genes in macrophages.","authors":"Kyu-Seon Oh, Mahamat Babagana, Sayantan Chakraborty, Mohammad Aqdas, Alicja Pacholewska, Daisy Dahiya, Michael Bustin, Myong-Hee Sung","doi":"10.1093/jimmun/vkag256","DOIUrl":"10.1093/jimmun/vkag256","url":null,"abstract":"The expression, localization, and secretion of certain chromatin proteins are tightly regulated in response to inflammatory challenges or tissue damage. High mobility group (HMG) nucleosome-binding proteins can translocate out of the nucleus to act as alarmins in immune cell communications. The consequences of nuclear depletion of HMGs in genome organization and gene regulation are not understood in the context of innate immunity. Here, we report alterations of tissue-specific macrophage transcriptome using a genetic knockout (KO) of HMGN1 and HMGN2, an HMGN double knockout mouse line. Lack of both HMGN proteins disrupted the expression of key macrophage genes, including those encoding MHCs, M-CSF, and ApoE, as well as acute responses to LPS, in a sex-dependent manner. These transcriptional effects were associated with concomitant changes in chromatin accessibility, as profiled by an assay for transposase accessible chromatin by sequencing, in regulatory sites distal and proximal to the corresponding genes. These findings highlight the importance of macrophage HMGNs in maintaining tissue-specific gene expression and supporting inflammatory responses.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Arid2 regulates peripheral B cell maturation and germinal-center responses in vivo. Arid2在体内调节外周B细胞成熟和生发中心反应。

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag247

Rachel L Paolini, Sarah M Zimmerman, Sadra Marjai, Sofia R Smith, Pei-Yu Chen, George P Souroullas

{"title":"Arid2 regulates peripheral B cell maturation and germinal-center responses in vivo.","authors":"Rachel L Paolini, Sarah M Zimmerman, Sadra Marjai, Sofia R Smith, Pei-Yu Chen, George P Souroullas","doi":"10.1093/jimmun/vkag247","DOIUrl":"10.1093/jimmun/vkag247","url":null,"abstract":"SWI/SNF chromatin remodeling complexes regulate gene expression during development and differentiation. These complexes exist in distinct forms, including the polybromo-associated BAF (PBAF) complex, defined by the ARID2 subunit. ARID2 is frequently mutated in B cell leukemias, but its role in normal B cell development remains unknown. Using Mb1-Cre and CD19-Cre conditional mouse models, we show that Arid2 is required for normal peripheral B-cell maturation. Early deletion with Mb1-Cre caused marked reductions in splenic T1 and T2 transitional B cells, follicular B cells, and recirculating B cells, whereas later deletion with CD19-Cre produced a milder follicular B cell phenotype but a similar reduction in transitional B cells. Bone-marrow progenitor and immature B cell populations were largely preserved, suggesting that the developmental defect emerges during peripheral transitional maturation and follicular B cell differentiation. Transcriptomic profiling of isolated pro-B, pre-B, and follicular B cells revealed that Arid2 loss caused progressive, stage-specific transcriptional dysregulation, including altered AP-1-associated programs and reduced B cell receptor-associated signaling in pre-B and follicular B cells. Functionally, mice with Mb1-Cre-mediated Arid2 deletion mice formed smaller germinal center B cell populations after immunization but maintained total and antigen-specific IgG responses and exhibited increased IgM responses. Together, these findings establish an important role for Arid2 in peripheral B cell maturation and germinal center responses.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential responses of liver versus lymphoid tissue DC to small extracellular vesicles generated by hepatic ischemia-reperfusion injury. 肝与淋巴组织DC对肝缺血再灌注损伤产生的细胞外小泡的差异反应。

IF 4 3区医学

Journal of immunology Pub Date : 2026-08-29 DOI: 10.1093/jimmun/vkag224

Cindy G Avalos-de Leon, Alan F Zahorchak, Suguru Mitsufuji, Bala Ramaswami, Hamza O Yazdani, Yannis Hadjiyannis, Geoffrey Camirand, David A Geller, Angus W Thomson

{"title":"Differential responses of liver versus lymphoid tissue DC to small extracellular vesicles generated by hepatic ischemia-reperfusion injury.","authors":"Cindy G Avalos-de Leon, Alan F Zahorchak, Suguru Mitsufuji, Bala Ramaswami, Hamza O Yazdani, Yannis Hadjiyannis, Geoffrey Camirand, David A Geller, Angus W Thomson","doi":"10.1093/jimmun/vkag224","DOIUrl":"10.1093/jimmun/vkag224","url":null,"abstract":"Hepatic ischemia-reperfusion (I/R) injury triggers release of small extracellular vesicles (sEVs) that can function as systemic conveyors of inflammatory signals. While sEV-mediated immune cell modulation has been studied extensively in vitro, knowledge is based largely on sEVs derived from cultured cells, rather than injured tissues. Consequently, the immunological impact of liver I/R-sEVs is poorly understood. Here, we combined in vitro and in vivo approaches with sEVs purified from mouse livers subjected to I/R to define their influence on dendritic cells (DCs). In vitro, in contrast to sham-sEVs, I/R-sEVs activated syngeneic bone marrow-derived DCs (BMDCs), inducing upregulation of costimulatory molecules and enhancing their capacity to stimulate naive allogeneic T-cells. In contrast, liver DCs (LDCs) were refractory to liver I/R-sEV-mediated activation. This differential responsiveness may in part reflect greater I/R-sEV internalization by BMDCs. To assess in vivo relevance, labeled sham or I/R-sEVs were administered intravenously. Following systemic delivery, syngeneic I/R-sEVs, but not sham-sEVs, accumulated in liver and spleen of otherwise naive mice exhibiting different patterns of uptake by immune cell populations. In the spleen, macrophages and B-cells were the principal I/R-sEV-acquiring populations, whereas in the liver, sEV uptake was dominated by macrophages and neutrophils. Additionally, while splenic DCs showed increased expression of activation markers and T-cell stimulatory activity following exposure to I/R-sEVs, LDCs were unresponsive. These findings identify liver-I/R-sEVs as promotors of extra-hepatic DC maturation/activation, whereas liver-resident DCs were refractory to I/R-sEV stimulation. The findings have implications for regulation of inflammatory responses following liver I/R injury.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0