Journal of immunology最新文献_第10页

T cell immunity to SARS-CoV-2 vaccination in inflammatory bowel disease patients treated with anti-cytokine biologics. 抗细胞因子生物制剂治疗炎症性肠病患者对SARS-CoV-2疫苗接种的T细胞免疫

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag173

Michelle W Cheung, Jenny D Choi, Joanne M Stempak, Vinod Chandran, Mark S Silverberg, Tania H Watts

{"title":"T cell immunity to SARS-CoV-2 vaccination in inflammatory bowel disease patients treated with anti-cytokine biologics.","authors":"Michelle W Cheung, Jenny D Choi, Joanne M Stempak, Vinod Chandran, Mark S Silverberg, Tania H Watts","doi":"10.1093/jimmun/vkag173","DOIUrl":"10.1093/jimmun/vkag173","url":null,"abstract":"Anti-TNF and anti-IL-12/IL-23 are commonly used therapies for immune-mediated inflammatory diseases (IMIDs), including inflammatory bowel disease (IBD). Although several studies have shown intact T cell responses following 2 to 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in biologics treated IMID patients, our group previously reported increased waning of T cell responses at 3-4 mos following the second vaccine dose in IMID patients compared to healthy controls, raising the possibility that a suboptimal initial T cell response could impact long term immunity. Here, to reduce patient heterogeneity, we focused only on IBD patients and further investigated T cell responses in vaccinated, untreated and biologics treated IBD patients compared to healthy controls. Following 1 vaccine dose, we observed a decreased frequency of Spike-reactive Th1 polarized cells and an increased frequency of Th2 cells in the IBD patients in general, relative to healthy controls. Additionally, IBD patients exhibited increased waning of Spike-specific cytokine T cell responses after 2 doses of vaccine. We also observed IBD-treatment specific effects. Spike-specific IL-2 secretion from anti-TNF or anti-IL-12/IL-23-treated patients' T cells was lower than from untreated patients following 1 dose of vaccine. However, single-cell RNA-sequencing of Spike-responsive T cells from anti-TNF and anti-IL-12/IL-23 treated IBD patients and healthy controls 2-4 wk after 2 or 3 vaccine doses revealed no major differences in T cell subsets, transcriptomes or TCR diversity. Thus, despite some evidence of impaired primary T cell responses, Spike-reactive T cells in patients treated with anti-TNF or anti-IL-12/IL-23 appear indistinguishable from healthy controls following a full vaccine course.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620388","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

Unconventional functions of natural killer cells in homeostasis and disease. 自然杀伤细胞在体内平衡和疾病中的非常规功能。

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag148

Anusha Anukanth, Stephen N Waggoner

引用次数: 0

Rag1-based time-stamp tracing of T-cell developmental origins. 基于rag1的时间戳追踪t细胞发育起源。

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag154

Menglin Jiang, Yichao Li, Xinying Zong, Xiaolei Hao, Clifford Guy, Wojciech Rosikiewicz, Minghong He, Lu Bai, Wenjun Huang, Vivek Choudhary, Yong Cheng, Yongqiang Feng

{"title":"Rag1-based time-stamp tracing of T-cell developmental origins.","authors":"Menglin Jiang, Yichao Li, Xinying Zong, Xiaolei Hao, Clifford Guy, Wojciech Rosikiewicz, Minghong He, Lu Bai, Wenjun Huang, Vivek Choudhary, Yong Cheng, Yongqiang Feng","doi":"10.1093/jimmun/vkag154","DOIUrl":"10.1093/jimmun/vkag154","url":null,"abstract":"The postnatal T‑cell pool comprises cells at diverse developmental stages, complicating efforts to resolve T‑cell differentiation, maturation, and long‑term adaptation. To address this challenge, we developed Rag1‑mediated time-stamp tracing, a genetic strategy that enables time‑resolved tracking of T‑cell developmental origins. We validate the specificity and temporal resolution of this approach across multiple analytical platforms, including flow cytometry, imaging, and single‑cell multiomics. Applying this strategy to thymic regulatory T (Treg) cell development, we show that time-stamp tracing resolves distinct phases of Treg cell induction, maturation, and long‑term adaptation within heterogeneous populations. This analysis identifies precursor populations for thymic Treg cell induction, uncovers a maturation program in nascent Treg cells marked by CD73 upregulation and progressive DNA hypomethylation at Treg cell-specific loci, and distinguishes long‑lived mature Treg cells characterized by activation and clonal expansion. Together, these findings establish Rag1‑based time-stamp tracing as a versatile and unbiased approach for resolving T‑cell developmental origins across immunological contexts.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630694","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

Binding of death receptor 3 (DR3) to intracellular TRADD and TRAF2 is independent of its natural ligand, TL1A. 死亡受体3 （DR3）与细胞内TRADD和TRAF2的结合独立于其天然配体TL1A。

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag194

Weiyong Sun, Bryce G Johnson, Praveen K Veerasubramanian, Kristin Rockwell, Theresa A Dickinson, Ruth F Sommese, Fridrik J Karlsson

{"title":"Binding of death receptor 3 (DR3) to intracellular TRADD and TRAF2 is independent of its natural ligand, TL1A.","authors":"Weiyong Sun, Bryce G Johnson, Praveen K Veerasubramanian, Kristin Rockwell, Theresa A Dickinson, Ruth F Sommese, Fridrik J Karlsson","doi":"10.1093/jimmun/vkag194","DOIUrl":"10.1093/jimmun/vkag194","url":null,"abstract":"The TNF‑like cytokine TL1A is a key regulator of immune responses through engagement of its receptor, death receptor 3 (DR3), and has emerged as a therapeutic target in inflammatory diseases. Prevailing models propose that TL1A binding initiates recruitment of adaptor proteins to DR3, leading to downstream signaling. Here, we investigated proximal DR3 signaling events and found that the adaptor proteins TRADD and TRAF2 associate with DR3 independently of TL1A stimulation in both TF‑1 cells and primary human CD4+ T cells. In contrast, TL1A stimulation was strictly required for activation of NF‑κB signaling, including IκBα degradation and downstream ubiquitination events. These findings indicate that DR3 can exist in a preassembled adaptor complex prior to ligand engagement and suggest a revised model in which TL1A binding confers signaling competence rather than initiating adaptor recruitment. We propose a structurally informed, hypothesis‑generating model in which ligand engagement promotes higher‑order organization of prebound signaling components to enable downstream signal transduction. Together, our results refine current understanding of TL1A/DR3 signaling by decoupling adaptor assembly from ligand‑dependent signal activation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603822","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

Modeling pathogenic B cell function in experimental autoimmune encephalomyelitis. 实验性自身免疫性脑脊髓炎致病性B细胞功能模型

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag163

Mohan Kumar, Connor R Wilhelm, Alexander W Boyden

{"title":"Modeling pathogenic B cell function in experimental autoimmune encephalomyelitis.","authors":"Mohan Kumar, Connor R Wilhelm, Alexander W Boyden","doi":"10.1093/jimmun/vkag163","DOIUrl":"10.1093/jimmun/vkag163","url":null,"abstract":"Success of B cell depletion therapy in multiple sclerosis (MS), an immune-mediated demyelinating disease of the central nervous system, places B cells and their functions center stage in efforts to fully understand pathogenesis. Historically, MS animal models of experimental autoimmune encephalomyelitis have featured B cell-independent disease driven by CD4 T cells activated against central nervous system myelin protein epitopes and have provided many insights into autoreactive T cell biology in the context of neuroinflammation and demyelination. Meanwhile, B cells' growing significance in MS necessitated the development of B cell-dependent experimental autoimmune encephalomyelitis models, which have allowed for critical exploration into pathogenic B cell functions during immune-mediated demyelinating disease, including cytokine and antibody production, as well as antigen presentation to autoreactive CD4 T cells. These advances represent an important arena for investigating MS pathogenesis. In this review, we summarize the various approaches taken to engage pathogenic B cells in animal models of MS.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421653","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

Gut microbial composition modulates endogenous food-specific CD4+ T cells in food allergy. 肠道微生物组成在食物过敏中调节内源性食物特异性CD4+ T细胞。

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag172

Alexa R Weingarden, Flannery S Dahlberg, Caroline N Broude, Xiandong Meng, Sunit Jain, Allison M Weakley, Ashley V Cabrera, Thamotharampillai Dileepan, Michael A Fischbach, Marc K Jenkins

{"title":"Gut microbial composition modulates endogenous food-specific CD4+ T cells in food allergy.","authors":"Alexa R Weingarden, Flannery S Dahlberg, Caroline N Broude, Xiandong Meng, Sunit Jain, Allison M Weakley, Ashley V Cabrera, Thamotharampillai Dileepan, Michael A Fischbach, Marc K Jenkins","doi":"10.1093/jimmun/vkag172","DOIUrl":"10.1093/jimmun/vkag172","url":null,"abstract":"The growing food allergy epidemic is thought to be related to changing environmental factors, particularly changes in the gut microbiome. While prior work has demonstrated that food allergy can be modulated by gut microbes, little is known about how food allergen-specific CD4+ T cells are affected by gut microbial composition. Here, we report that food allergy severity differs between mice obtained from 2 different specific pathogen-free mouse vendors (Jackson Labs [Jax] and Taconic Biosciences [Tac]). Mice from Tac develop diarrhea and anaphylaxis after fewer allergen exposures than mice from Jax. Using food allergen peptide: MHCII tetramers, we also find that Tac mice have fewer allergen-specific regulatory T cells in the small intestine compared to mice from Jax with concomitant increase in allergen-specific Th2 cells. In addition, Tac mice have increased intestinal permeability. Increased food allergy severity, phenotype of allergen-specific T cells, and increased gut permeability were transferable to Jax animals via co-housing, which corresponded to a shift in Jax microbial communities towards those found in Tac mice. Our findings demonstrate that food allergen-specific Treg cells can be modulated by gut microbial community composition, which in turn is correlated to food allergy severity.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630725","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

A novel Vδ1 engager targeting CD19 enhances human Vδ1 γδ T cell responses against CLL and CD19+ hematological malignancies. 一种新的靶向CD19的Vδ1接合剂增强了人Vδ1 γδ T细胞对CLL和CD19+血液恶性肿瘤的应答。

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag167

Shefali A Bhumbra, Robert Good, Antara Banerjee, Tyreese Hines, Katherine J Seidl, Jessica Strid, Andrew J Hutton

{"title":"A novel Vδ1 engager targeting CD19 enhances human Vδ1 γδ T cell responses against CLL and CD19+ hematological malignancies.","authors":"Shefali A Bhumbra, Robert Good, Antara Banerjee, Tyreese Hines, Katherine J Seidl, Jessica Strid, Andrew J Hutton","doi":"10.1093/jimmun/vkag167","DOIUrl":"https://doi.org/10.1093/jimmun/vkag167","url":null,"abstract":"γδ T cells are associated with favorable outcomes in many cancers likely through a mechanism of stress-directed cytotoxicity and antitumor cytokine production. Vδ1 γδ T cells are especially promising for immunotherapy due to their broad stress recognition and resistance to activation-induced cell death. Here, we generate a CD19 engager incorporating a novel Vδ1 binding moiety as proof-of-concept for treating CD19+ cancers, including Chronic Lymphocytic Leukemia (CLL). In vitro studies validated Vδ1/CD19 engager-directed cellular binding and Vδ1 activation, where 41BB, CD25 and CD107a were upregulated on Vδ1 T cells following co-culture with CD19+ cancer cell lines and Vδ1/CD19 engager treatment. Ex vivo studies demonstrated engager-mediated Vδ1 T cell proliferation within healthy PBMC cultures that also correlated to basal Vδ1 CD27 expression. Engager-treated PBMCs demonstrated enhanced cytotoxicity against CD19+ cell lines and primary CLL B cells, with minimal killing of healthy B cells and without inducing excessive cytokine release compared with a CD3/CD19 engager. Phenotypic analysis suggested engager treatment encourages maturation of naive Vδ1 T cells, where upregulation of NKG2D, DNAM-1, CD96, CD2, ICOS, and PD-1 were observed, and in culture with cancerous cells, downregulation of CD27 and CD45RA alongside granzyme-B upregulation. Blockade of such co-receptors reduced Vδ1 cytotoxicity following engager treatment whereas co-receptor stimulation modestly enhanced Vδ1 activation. These data suggest that Vδ1/CD19 engager treatment enhances anti-tumoral Vδ1-capabilities while maintaining sufficient dependency on stress ligand availability, supporting selective targeting of malignant over healthy cells. Overall, our data support the rationale for Vδ1-directed immunotherapies and uncovers potential mechanisms that enhance Vδ1 cytotoxic responses against CD19+ cancers.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455724","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

Toll-like receptor responses are shaped by distinct MAPK activation profiles. toll样受体反应是由不同的MAPK激活谱形成的。

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag180

Nada Elhadedy, Areej Alotaibi, Lynn McGarry, Ruaidhrí J Carmody

{"title":"Toll-like receptor responses are shaped by distinct MAPK activation profiles.","authors":"Nada Elhadedy, Areej Alotaibi, Lynn McGarry, Ruaidhrí J Carmody","doi":"10.1093/jimmun/vkag180","DOIUrl":"https://doi.org/10.1093/jimmun/vkag180","url":null,"abstract":"Toll-like receptors (TLRs) are key sensors of infection and injury, and are critical inducers of inflammation. TLR-induced activation of the NF-κB and MAPK pathways promotes the secretion of mediators of inflammation such as cytokines and chemokines. Control of cytokine production is critically important, as unnecessary inflammatory responses can lead to tissue damage, while insufficient inflammatory responses can lead to susceptibility to infection. Previous studies showed that TLR4 uses distinct NF-κB and MAPK activation properties to discriminate between low and high concentrations of ligand, triggering cytokine production only at ligand concentrations that activate both pathways. The switch-like activation of MAPKs by TLR4 establishes an inflammatory threshold for ligand concentrations that facilitates threat discrimination. Using murine macrophages, we reveal that MAPK activation properties are TLR-specific, and that switch-like MAPK activation is not a general feature of all TLRs. Consequently, certain TLRs do not have an inflammatory threshold of ligand concentration and may not effectively filter signal from noise. The activation properties of the ERK pathway, rather than messenger RNA levels, dictate the patterns of TNFα cytokine secretion for all TLRs examined. We demonstrate that the TLR4 inflammatory threshold can be modulated by costimulation with granulocyte-macrophage colony-stimulating factor in an ERK-dependent manner. We show that deletion of BCL-3 changes the TLR4-induced ERK pathway activation properties from switch-like to gradual and lowers the activation threshold. We reveal that different TLRs have different capacities to discriminate threats based on ligand concentration, and that ERK pathway activation properties can be altered to change the cellular decision to initiate inflammation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536307","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

mTECs and B cells form a thymic microniche associated with B-cell licensing. mtec和B细胞形成与B细胞许可相关的胸腺微细胞。

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag185

Ryan J Martinez, Adrianna M Rivera-León, Avrora Nikolaeva, Kelsey Esposito, Matouš Vobořil, Kyra Boorsma Bergerud, Miriam Arroyo, Andrew C Nelson, Micheal A Farrar, Sean I Tracy, Andrea Reboldi, Brian T Fife, Kristin A Hogquist

{"title":"mTECs and B cells form a thymic microniche associated with B-cell licensing.","authors":"Ryan J Martinez, Adrianna M Rivera-León, Avrora Nikolaeva, Kelsey Esposito, Matouš Vobořil, Kyra Boorsma Bergerud, Miriam Arroyo, Andrew C Nelson, Micheal A Farrar, Sean I Tracy, Andrea Reboldi, Brian T Fife, Kristin A Hogquist","doi":"10.1093/jimmun/vkag185","DOIUrl":"10.1093/jimmun/vkag185","url":null,"abstract":"Thymic B cells rely on T cells and type-III IFN (IFN-λ) signaling for class switch recombination and effective licensing as APCs, a process essential for their role in establishing central T-cell tolerance. IFN-λ is produced exclusively by a subset of medullary thymic epithelial cells (mTECs); however, the spatial layout between B cells and IFN-λ-producing mTECs remain unclear. Here, we studied the distribution of thymic B cells and IFN-λ+ mTECs, alongside other mTEC populations, to better understand the niche required for thymic B-cell licensing. Using 26 target multiplex immunofluorescence imaging of the thymus, we identified populations of naïve B cells, licensed B cells, plasmacytoid dendritic cells, plasma cells, mTECs, and mimetic mTECs within the thymus. Spatial analysis revealed licensed B cells closely interacted with both IFN-λ+ mTEC and GP2+ microfold mTECs, with transcriptional analysis predicting CCL20-CCR6-mediated B-cell interactions with microfold and IFN-λ+ mTECs. However, studies in CCR6-deficient mice showed CCR6-CCL20 interaction was not required for B-cell licensing. To further investigate the role of GP2+ microfold mTECs in B-cell licensing, we studied the NOD/ShiLtJ mouse model, which we confirmed to have a natural reduction in microfold mTECs. Interestingly, the thymic B cells in NOD mice demonstrated reduced licensing, which was attributed to reductions in IFN-λ receptor expression on thymic B cells. These data indicate that microfold mTECs modulate the capacity of thymic B cells to undergo IFN-λ-induced licensing.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471026","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

The discovery and roles of type 2 innate lymphoid cells. 2型先天淋巴样细胞的发现及其作用。

IF 4 3区医学

Journal of immunology Pub Date : 2026-07-10 DOI: 10.1093/jimmun/vkag104

Jenny Mjösberg, Itziar Martinez-Gonzalez

引用次数: 0