Journal of immunology最新文献

{"title":"Knee osteoarthritis (OA)-related phenotypes of myeloid-derived suppressor cells (MDSCs) is mediated by infrapatellar fat pat (IPFP)-derived factors in a body mass index (BMI)-dependent manner and positively correlates with IPFP-derived adiponectin levels.","authors":"Varote Shotelersuk, Panjana Sengprasert, Somkiat Phutinart, Patchanika Hengtrakool, Sujinthra Pimthanom, Mana Taweevisit, Anand Prugmahachaikul, Srihatach Ngarmukos, Aree Tanavalee, Tanapat Palaga, Rangsima Reantragoon","doi":"10.1093/jimmun/vkaf213","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf213","url":null,"abstract":"<p><p>Osteoarthritis (OA) is characterized by cartilage destruction and immune cell infiltration, of which include myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to expand in obese patients with OA. Therefore, we aimed to investigate the role of obesity on MDSC function in knee OA patients. We isolated MDSCs from infrapatellar fat pads (IPFPs) of knee OA patients and evaluated MDSCs both quantitatively and qualitatively. We also performed a transcriptomic analysis of IPFP-isolated MDSCs of low, moderate and high body mass index (BMI) patients. In vitro IPFP-cultured media (CM)- and/or synovial tissues (ST)-CM-treated monocyte-derived MDSCs were evaluated for gene expression, immunosuppressive function and osteoclastogenesis potential. Cytokine and adipokine screening of IPFP-CM and ST-CM used for treatment were also screened. MDSC abundance and cytokine expression correlated with increasing BMI. Transcriptomic analysis revealed upregulation of numerous genes in OA-related pathways in IPFP-isolated MDSCs of moderate and high BMI patients, but downregulated in low BMI patients. In vitro assays demonstrate upregulation of OA-related genes, increased cytokine production, impaired immunosuppressive function and increased osteoclastogenesis potential of monocyte-derived MDSCs in a BMI-dependent manner, predominantly from IPFP-CM. IPFP-derived adiponectin levels correlated significantly with BMI status; interleukin (IL)-1β, MCP1, IL-17A, IL-12p70, and IL-8 levels that were secreted from monocyte-derived MDSCs in response to IPFP-CM treatment; and immunosuppressive function. Obesity may be driving knee OA pathology via metabolic changes in IPFPs. These changes directly and indirectly affect MDSC phenotype and function, of which include phenotypes that favor OA pathology.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091878","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}

{"title":"Altered distribution of tissue galectins correlates with mucosal dysregulation in SIV infection.","authors":"Thomas A Premeaux, Stephen T Yeung, Samuel D Johnson, Preeti Moar, Siddappa N Byrareddy, Lishomwa C Ndhlovu","doi":"10.1093/jimmun/vkaf200","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf200","url":null,"abstract":"<p><p>The intestinal mucosa in individuals with chronic human immunodeficiency virus (HIV) infection remains a site of viral persistence and immune dysregulation, even with prolonged suppressive antiretroviral therapy (ART). While biomarkers of mucosal damage and microbial translocation offer valuable correlative insights, the underlying mechanisms remain incompletely understood. Immunoregulatory galectins are implicated in HIV persistence and pathogenesis and play critical roles in intestinal inflammation and host-microbiome homeostasis. Here, we leveraged archival samples and data from an anti-α4β7 immunotherapy study of simian immunodeficiency virus (SIV)-infected rhesus macaques to investigate the relationships between circulating and gut mucosal galectins 1, 3, and 9, and barrier integrity, by tracking levels of tight junction proteins, and SIV viral load assessment of RNA and DNA levels in tissues. Elevated plasma levels of galectin-9 during peak viremia, ART suppression, ART interruption, and at necropsy were significantly correlated with SIVgag DNA levels in the ascending colon during necropsy. Several galectins were significantly reduced in the ascending colon and duodenum in ART-treated SIV-infected macaques compared to viremic animals and were related to tight junction disruptions. These findings suggest mucosal SIV burden and impaired gut integrity may be influenced by changes due to circulating and tissue galectins, making them potential therapeutic targets to restore gut homeostasis.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091843","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}

{"title":"Dysregulation of complement components associated with inflammation and coagulation in virally suppressed people living with HIV.","authors":"Natalie T Subia, Thomas K Awamura, Logan S Dean, Keona Loftis, Louie Mar Gangcuangco, Iain MacPherson, Sandra Chang, Dominic C Chow, Cecilia M Shikuma, Juwon Park","doi":"10.1093/jimmun/vkaf227","DOIUrl":"10.1093/jimmun/vkaf227","url":null,"abstract":"<p><p>Although the interplay between the complement system, platelets, and neutrophils has been considered a major contributor to inflammation and thrombogenicity, little attention has been directed toward understanding their roles in people living with human immunodeficiency virus (PLWH). We quantified and compared expression levels of complement components (C2, C3a, C5a, C9), markers for coagulation (vWF-A2, ADAMTS13, tissue factor (TF), protein C, fibrinogen), and neutrophil activation (MPO, MMP-9) in plasma between virally suppressed PLWH (n = 40) and people living without HIV (PLWoH; n = 39). Platelet and activated platelet (CD62P+ cells) counts in the plasma samples were examined by flow cytometry analysis. To determine whether PLWH's plasma promotes neutrophil extracellular traps (NETs) and whether C2 and C5a levels correlate with NET formation, an ex vivo NET assay was performed. PLWH showed significantly altered C2 and C5a levels in plasma that correlated strongly with protein C and MPO. C2 also showed a positive correlation with proinflammatory markers (SSA, SAP, IL-1β, and VEGF). Furthermore, HIV status was a significant predictor of C2 and C5a levels. CD62P expression on platelets was significantly increased in PLWH. In addition, treatment of healthy neutrophils with PLWH's plasmapromoted NET formation, and this effect was inhibited by C5aR antibody treatment and platelet removal. These data suggest that activated platelets and soluble factors, such as higher C5a levels, contribute to NET formation in PLWH. Our findings provide evidence of complement dysregulation associated with inflammation and coagulation in PLWH. Altered soluble factors and platelet activation promote NET formation, potentially driving age-related non-AIDS comorbidities (NACMs).</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091815","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}

{"title":"Platelet-like anucleate cell fragments mediate wound healing and immune response in the sea star Patiria pectinifera.","authors":"Kota Minakata, Mizuki Taguchi, Akihiro Tame, Ritsu Kuraishi, Ryohei Furukawa","doi":"10.1093/jimmun/vkaf246","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf246","url":null,"abstract":"<p><p>Blood coagulation and immune responses have long been considered as discrete processes. However, recent studies have revealed that mammalian platelets play a critical role in immune regulation in addition to their well-established role in hemostasis. This dual functionality suggests an evolutionary link between platelets and invertebrate blood cells that contributes to both immune responses and wound healing. However, megakaryocytes, the precursor cells of platelets, are unique to mammals. It is widely believed that invertebrates lack a mechanism for producing anucleate cell fragments similar to platelets. Here, we report the discovery of anucleate cell fragments in the coelomic fluid of the sea star Patiria pectinifera. Detailed scanning electron microscopy revealed that the anucleate cell fragments exhibit both morphological and functional similarities to mammalian platelets. These cell fragments, which are derived from immune cells (coelomocytes), accumulate at wound sites, aggregate with coelomocytes, and serve as major sources of extracellular vesicles. Furthermore, extracellular vesicles released by these fragments not only promote aggregate formation in response to foreign substances but also transfer their contents into coelomocytic cytoplasm. Our findings suggest that a mechanism for generating anucleate cell fragments with platelet-like functions already exists in invertebrate immune cells. This study provides new insights into the evolutionary origins and broader immunological significance of platelets.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091969","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}

{"title":"Computing the inducibility of broadly neutralizing antibodies under a context-dependent model of affinity maturation: applications to sequential vaccine design.","authors":"Joseph Mathews, Elizabeth Van Itallie, Yongkang Li, Kevin Wiehe, Scott C Schmidler","doi":"10.1093/jimmun/vkaf234","DOIUrl":"10.1093/jimmun/vkaf234","url":null,"abstract":"<p><p>A key challenge in B-cell lineage-based vaccine design is understanding the \"inducibility\" of target neutralizing antibodies-the ability of these antibodies to be elicited by presentation of an immunogen. Induction relies on a combination of stochastic diversification and immunogen-based selection, and as a result is heavily dependent on the probabilistic accessibility of induction pathways. We explored inducibility using a detailed stochastic model of the somatic hypermutation process-which captures the critical \"context-dependence\" of sequence mutation rates-coupled to a stochastic population model for B-cell clonal maturation. The model is used to calculate inducibilities for a set of critical mutations required by the HIV broadly neutralizing antibody (bnAb) CH235.12. The results provide insight into barriers to the elicitation of HIV bnAbs and explain experimental results observed in mouse models. Our models enable detailed analysis of maturation pathway probabilities, allowing us to identify opportunities for the design of boosting immunogens aimed at elicitation of CH235.12 via a sequential vaccination regimen.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091854","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}

{"title":"Evolving the cutting edge: enhancing author flexibility and elevating peer recognition.","authors":"Luis J Montaner, Gail A Bishop","doi":"10.1093/jimmun/vkaf241","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf241","url":null,"abstract":"","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091881","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}

{"title":"Type 1 regulatory cells suppress T-cell cytotoxicity to alleviate liver injury during acute hepatitis B virus infection in mice.","authors":"Xiaofang Li, Wenxuan Sun, Qianyu Wang, Huixi Zhang, Xiaolan Xu, Yuheng Shi, Hong Chen, Xiaojiao Zhuang, Jiangxia Liu, Jianhua Li","doi":"10.1093/jimmun/vkaf229","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf229","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) exclusively infects hepatocytes and produces large quantities of subviral particles containing its surface antigen (HBsAg). T cells play a central role in controlling HBV infection but can also mediate liver injury and contribute to disease progression. However, the mechanisms that regulate T-cell responses to eliminate the virus without causing immunopathology during acute HBV infection remain poorly defined. In this study, we established acute HBV infection models in mice by delivering the HBV genome to the liver via hydrodynamic injection or high-dose adenoviral vector administration. Single-cell RNA sequencing was performed to characterize the heterogeneity of HBsAg-specific CD4+ T cells, revealing distinct functional subsets, including follicular helper (Tfh), cytotoxic, and type 1 regulatory (Tr1) cells. These subsets were further validated by flow cytometry using representative phenotypic markers. Our findings demonstrate that Tr1 cells attenuate the cytotoxicity of both CD4+ and CD8+ T cells in response to HBsAg. Neutralization of interleukin-10 (IL-10) impaired Tr1-mediated suppression of cytotoxic T-cell responses. Notably, IL-10 deficiency in Tr1 cells led to substantial liver injury without enhancing HBsAg clearance. Together, these results highlight the critical function of Tr1 cells in safeguarding against liver immunopathology by modulating T-cell cytotoxicity during acute HBV infection in mice.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029473","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}

{"title":"CXCR6 promotes dermal CD8+ T cell survival and transition to long-term tissue residence.","authors":"Taylor A Heim, Ochapa Ibrahim, Ziyan Lin, Austin C Schultz, Maria M Steele, Tenny Mudianto, Amanda W Lund","doi":"10.1093/jimmun/vkaf219","DOIUrl":"10.1093/jimmun/vkaf219","url":null,"abstract":"<p><p>Tissue resident memory T cells (TRM) provide protection against local re-infection, and yet the interstitial signals that govern their formation and persistence remain poorly defined. Here, we show that antigen-dependent induction of the chemokine receptor CXCR6, is a conserved adaptation to peripheral tissue infiltration that promotes TRM formation after viral infection. Deficient TRM formation in the absence of CXCR6 was not explained by trafficking as CXCR6 was not required for tissue entry, was dispensable for the early accumulation of antigen-specific CD8+ T cells in skin, and did not restrain their exit. Single cell sequencing indicated that Cxcr6-/- CD8+ T cells were competent to acquire a transcriptional program of residence and TRM that formed were equally functional compared to their WT counterparts when reactivated greater than 100 days post primary infection. The reduction in Cxcr6-/- CD8+ T cells at memory time points, was associated with impaired redox homeostasis, antioxidant capacity, and increased rates of apoptosis in the dermis during the transition from effector to resident memory. Thus, CXCR6 promotes the adaptation of T cells as they engage antigen in tissue to increase the probability of survival, memory differentiation, and long-term residence.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000787","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}

{"title":"LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia.","authors":"Chi G Weindel, Aja K Coleman, Lily M Ellzey, Sandeep Kumar, Sara L Chaisson, Jacob R Davis, Kristin L Patrick, Robert O Watson","doi":"10.1093/jimmun/vkaf215","DOIUrl":"10.1093/jimmun/vkaf215","url":null,"abstract":"<p><p>Mounting evidence supports a critical role for central nervous system (CNS) glial cells in neuroinflammation and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), as well as neurovascular ischemic stroke. Previously, we found that loss of the PD-associated gene leucine-rich repeat kinase 2 (Lrrk2) in macrophages, peripheral innate immune cells, induced mitochondrial stress and elevated basal expression of type I interferon (IFN) stimulated genes (ISGs) due to chronic mitochondrial DNA engagement with the cGAS/STING DNA sensing pathway. Here we report that loss of LRRK2 results in a paradoxical response in microglial cells, a CNS-specific macrophage population. In primary murine microglia and microglial cell lines, loss of Lrrk2 reduces tonic IFN signaling leading to a reduction in ISG expression. Consistent with reduced type I IFN, mitochondria from Lrrk2 KO microglia are protected from stress and have elevated metabolism. These protective phenotypes involve upregulation of NRF2, an important transcription factor in the response to oxidative stress and are restricted by LRRK2 kinase activity. Collectively, these findings illustrate a dichotomous role for LRRK2 within different immune cell populations and give insight into the fundamental differences between immune regulation in the CNS and the periphery.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000697","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}

{"title":"CD55hi MAIT cells with elevated cytokine secretion and activation markers serve as potential diagnostic indicators in Sjögren's disease.","authors":"Yiming Gao, Hanxi Luo, Bohao Yang, Xuzheng Song, Ziqi Xiong, Ayibaota Bahabayi, Zhonghui Zhang, Chen Liu","doi":"10.1093/jimmun/vkaf226","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf226","url":null,"abstract":"<p><p>Mucosal-associated invariant T (MAIT) cells play a vital role in immune responses, yet their involvement in autoimmune diseases such as Sjögren's disease (SjD) remains unclear. CD55, a key regulator of complement activation, influences immune cell function. This study investigates CD55 expression on MAIT cells in SjD patients and healthy controls, evaluating its potential as a diagnostic marker. Flow cytometry was used to assess CD55 expression on MAIT cell subsets, including CD4-CD8+, CD4+CD8-, double-positive (DP), and double-negative (DN), in peripheral blood from SjD patients and healthy controls. Functional markers (PD-1, CD83, and CD44), cytokine production (TNF-α, IFN-γ, IL-17, IL-22), and granzyme B (GZMB) secretion were analyzed following 5-OP-RU and brefeldin A stimulation. Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic utility of CD55 expression. CD55 was highly expressed on MAIT cells, with the highest expression intensity observed in DP MAIT cells, followed by CD4+CD8- MAIT and CD4-CD8+ MAIT, with the lowest expression found in DN MAIT cells. CD55hi MAIT cells demonstrated significantly higher percentages of PD-1+, CD83+, and CD44+ cells, along with enhanced cytokine and GZMB secretion following stimulation. In SjD patients, CD55 expression was significantly upregulated in MAIT cells. ROC analysis indicated that CD55hi MAIT cells have potential diagnostic value for SjD. CD55 is highly expressed on MAIT cells, with upregulation in SjD patients correlating with inflammation and autoantibodies, suggesting CD55hi MAIT cells as a potential diagnostic marker for SjD.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992647","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}