Journal of immunology最新文献_第8页

Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development. 内质网应激反应介质 IRE-1α 促进宿主树突状细胞在移植物抗宿主疾病发展中的作用

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2300616

Hee-Jin Choi, Yongxia Wu, Brianyell McDaniel Mims, Allison Pugel, Chih-Hang Anthony Tang, Linlu Tian, Chih-Chi Andrew Hu, Xue-Zhong Yu

{"title":"Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development.","authors":"Hee-Jin Choi, Yongxia Wu, Brianyell McDaniel Mims, Allison Pugel, Chih-Hang Anthony Tang, Linlu Tian, Chih-Chi Andrew Hu, Xue-Zhong Yu","doi":"10.4049/jimmunol.2300616","DOIUrl":"10.4049/jimmunol.2300616","url":null,"abstract":"Allogeneic hematopoietic cell transplantation is an effective treatment for hematologic malignancies, but the complications such as graft-versus-host disease (GVHD) can limit its benefit. The conditioning regimens before transplant, including chemotherapy or irradiation, can trigger endoplasmic reticulum stress. IRE-1α is a major endoplasmic reticulum stress mediator that can further activate both spliced XBP-1 (XBP-1s) and regulated IRE-1-dependent decay (RIDD). IRE-1α-XBP-1s signaling controls dendritic cell (DC) differentiation and Ag presentation, crucial in GVHD progression. In this study, we used DC-specific XBP-1-deficient mice as donors or recipients and observed that XBP-1s was crucial for host DCs in the induction of GVHD but dispensable for the graft-versus-leukemia response. To specifically target IRE-1α in the host, we treated recipient mice with the IRE-1α inhibitor B-I09 for 3 d prior to bone marrow transplantation, which significantly suppressed GVHD development while maintaining the graft-versus-leukemia effect. XBP-1-deficient or BI09-treated recipients showed reduced DC survival after irradiation and bone marrow transplantation. Inhibition of IRE-1α also led to a reduction in DC alloreactivity, subsequently decreasing the proliferation and activation of allogeneic T cells. With further study using RIDD-deficient DCs, we observed that RIDD was also required for optimal DC activation. Taken together, XBP-1s and RIDD both promote host DC survival and alloreactivity that contribute to GVHD development.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306133","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

B Cells of Early-life Origin Defined by RAG2-based Lymphoid Cell Tracking under Native Hematopoietic Conditions. 在原生造血条件下通过基于 RAG2 的淋巴细胞追踪确定生命早期起源的 B 细胞

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2400072

Keiko Fujisaki, Shogo Okazaki, Shuhei Ogawa, Miyama Takeda, Eiji Sugihara, Kenichi Imai, Seiya Mizuno, Satoru Takahashi, Ryo Goitsuka

{"title":"B Cells of Early-life Origin Defined by RAG2-based Lymphoid Cell Tracking under Native Hematopoietic Conditions.","authors":"Keiko Fujisaki, Shogo Okazaki, Shuhei Ogawa, Miyama Takeda, Eiji Sugihara, Kenichi Imai, Seiya Mizuno, Satoru Takahashi, Ryo Goitsuka","doi":"10.4049/jimmunol.2400072","DOIUrl":"10.4049/jimmunol.2400072","url":null,"abstract":"During the perinatal period, the immune system sets the threshold to select either response or tolerance to environmental Ags, which leads to the potential to provide a lifetime of protection and health. B-1a B cells have been demonstrated to develop during this perinatal time window, showing a unique and restricted BCR repertoire, and these cells play a major role in natural Ab secretion and immune regulation. In the current study, we developed a highly efficient temporally controllable RAG2-based lymphoid lineage cell labeling and tracking system and applied this system to understand the biological properties and contribution of B-1a cells generated at distinct developmental periods to the adult B-1a compartments. This approach revealed that B-1a cells with a history of RAG2 expression during the embryonic and neonatal periods dominate the adult B-1a compartment, including those in the bone marrow (BM), peritoneal cavity, and spleen. Moreover, the BCR repertoire of B-1a cells with a history of RAG2 expression during the embryonic period was restricted, becoming gradually more diverse during the neonatal period, and then heterogeneous at the adult stage. Furthermore, more than half of plasmablasts/plasma cells in the adult BM had embryonic and neonatal RAG2 expression histories. Moreover, BCR analysis revealed a high relatedness between BM plasmablasts/plasma cells and B-1a cells derived from embryonic and neonatal periods, suggesting that these cell types have a common origin. Taken together, these findings define, under native hematopoietic conditions, the importance in adulthood of B-1a cells generated during the perinatal period.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317537","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

Distinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells. 生命早期扁桃体调节性 T 细胞的不同定位、转录谱和功能。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2300890

Shivali Verma, Marissa C Bradley, Joshua Gray, Pranay Dogra, Daniel P Caron, Sarah Maurrasse, Eli Grunstein, Erik Waldman, Minyoung Jang, Kalpana Pethe, Donna L Farber, Thomas J Connors

{"title":"Distinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells.","authors":"Shivali Verma, Marissa C Bradley, Joshua Gray, Pranay Dogra, Daniel P Caron, Sarah Maurrasse, Eli Grunstein, Erik Waldman, Minyoung Jang, Kalpana Pethe, Donna L Farber, Thomas J Connors","doi":"10.4049/jimmunol.2300890","DOIUrl":"10.4049/jimmunol.2300890","url":null,"abstract":"CD4+ regulatory T cells (Tregs) are key orchestrators of the immune system, fostering the establishment of protective immunity while preventing deleterious responses. Infancy and childhood are crucial periods of rapid immunologic development, but how Tregs mediate immune responses at these earliest timepoints of human life is poorly understood. In this study, we compare blood and tissue (tonsil) Tregs across pediatric and adult subjects to investigate age-related differences in Treg biology. We observed increased FOXP3 expression and proportions of Tregs in tonsil compared with paired blood samples in children. Within tonsil, early life Tregs accumulated in extrafollicular regions with cellular interactions biased toward CD8+ T cells. Tonsil Tregs in both children and adults expressed transcriptional profiles enriched for lineage defining signatures and canonical functionality compared with blood, suggesting tissue as the primary site of Treg activity. Early life tonsil Tregs transcriptional profiles were further defined by pathways associated with activation, proliferation, and polyfunctionality. Observed differences in pediatric tonsil Treg transcriptional signatures were associated with phenotypic differences, high proliferative capacity, and robust production of IL-10 compared with adult Tregs. These results identify tissue as a major driver of Treg identity, provide new insights into developmental differences in Treg biology across the human lifespan, and demonstrate unique functional properties of early life Tregs.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437010","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

CCL22 Induces the Polarization of Immature Dendritic Cells into Tolerogenic Dendritic Cells in Radiation-Induced Lung Injury through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 Signaling Pathway. CCL22通过CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1信号通路诱导辐射诱导的肺损伤中未成熟树突状细胞极化为耐受性树突状细胞

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2300718

Benbo Liu, Yilong Wang, Liping Ma, Guo Chen, Zhihua Yang, Maoxiang Zhu

{"title":"CCL22 Induces the Polarization of Immature Dendritic Cells into Tolerogenic Dendritic Cells in Radiation-Induced Lung Injury through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 Signaling Pathway.","authors":"Benbo Liu, Yilong Wang, Liping Ma, Guo Chen, Zhihua Yang, Maoxiang Zhu","doi":"10.4049/jimmunol.2300718","DOIUrl":"10.4049/jimmunol.2300718","url":null,"abstract":"Recruitment of immune cells to the injury site plays a pivotal role in the pathology of radiation-associated diseases. In this study, we investigated the impact of the chemokine CCL22 released from alveolar type II epithelial (AT2) cells after irradiation on the recruitment and functional changes of dendritic cells (DCs) in the development of radiation-induced lung injury (RILI). By examining changes in CCL22 protein levels in lung tissue of C57BL/6N mice with RILI, we discovered that ionizing radiation increased CCL22 expression in irradiated alveolar AT2 cells, as did MLE-12 cells after irradiation. A transwell migration assay revealed that CCL22 promoted the migration of CCR4-positive DCs to the injury site, which explained the migration of pulmonary CCR4-positive DCs in RILI mice in vivo. Coculture experiments demonstrated that, consistent with the response of regulatory T cells in the lung tissue of RILI mice, exogenous CCL22-induced DCs promoted regulatory T cell proliferation. Mechanistically, we demonstrated that Dectin2 and Nr4a2 are key targets in the CCL22 signaling pathway, which was confirmed in pulmonary DCs of RILI mice. As a result, CCL22 upregulated the expression of PD-L1, IL-6, and IL-10 in DCs. Consequently, we identified a mechanism in which CCL22 induced DC tolerance through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 pathway. Collectively, these findings demonstrated that ionizing radiation stimulates the expression of CCL22 in AT2 cells to recruit DCs to the injury site and further polarizes them into a tolerant subgroup of CCL22 DCs to regulate lung immunity, ultimately providing potential therapeutic targets for DC-mediated RILI.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296211","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

Inflammasomes at the Foundation of Inflammatory Cell Death Complexes. 炎症细胞死亡复合物的基础炎症小体

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2400288

Rebecca E Tweedell, Thirumala-Devi Kanneganti

引用次数: 0

Reappraising the Role of T Cell-Derived IFN-γ in Restriction of Mycobacterium tuberculosis in the Murine Lung. 重新评估 T 细胞产生的 IFN-γ 在限制小鼠肺部结核分枝杆菌中的作用

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2400145

Karolina Maciag, Courtney R Plumlee, Sara B Cohen, Benjamin H Gern, Kevin B Urdahl

引用次数: 0

Human Alveolar and Monocyte-Derived Human Macrophage Responses to Mycobacterium tuberculosis. 人类肺泡和单核细胞衍生的人类巨噬细胞对结核分枝杆菌的反应

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-07-15 DOI: 10.4049/jimmunol.2300885

Monica Campo, Kimberly A Dill-McFarland, Glenna J Peterson, Basilin Benson, Shawn J Skerrett, Thomas R Hawn

{"title":"Human Alveolar and Monocyte-Derived Human Macrophage Responses to Mycobacterium tuberculosis.","authors":"Monica Campo, Kimberly A Dill-McFarland, Glenna J Peterson, Basilin Benson, Shawn J Skerrett, Thomas R Hawn","doi":"10.4049/jimmunol.2300885","DOIUrl":"10.4049/jimmunol.2300885","url":null,"abstract":"Alveolar macrophages (AMs) and recruited monocyte-derived macrophages (MDMs) mediate early lung immune responses to Mycobacterium tuberculosis. Differences in the response of these distinct cell types are poorly understood and may provide insight into mechanisms of tuberculosis pathogenesis. The objective of this study was to determine whether M. tuberculosis induces unique and essential antimicrobial pathways in human AMs compared with MDMs. Using paired human AMs and 5-d MCSF-derived MDMs from six healthy volunteers, we infected cells with M. tuberculosis H37Rv for 6 h, isolated RNA, and analyzed transcriptomic profiles with RNA sequencing. We found 681 genes that were M. tuberculosis dependent in AMs compared with MDMs and 4538 that were M. tuberculosis dependent in MDMs, but not AMs (false discovery rate [FDR] < 0.05). Using hypergeometric enrichment of DEGs in Broad Hallmark gene sets, we found that type I and II IFN Response were the only gene sets selectively induced in M. tuberculosis-infected AM (FDR < 0.05). In contrast, MYC targets, unfolded protein response and MTORC1 signaling, were selectively enriched in MDMs (FDR < 0.05). IFNA1, IFNA8, IFNE, and IFNL1 were specifically and highly upregulated in AMs compared with MDMs at baseline and/or after M. tuberculosis infection. IFNA8 modulated M. tuberculosis-induced proinflammatory cytokines and, compared with other IFNs, stimulated unique transcriptomes. Several DNA sensors and IFN regulatory factors had higher expression at baseline and/or after M. tuberculosis infection in AMs compared with MDMs. These findings demonstrate that M. tuberculosis infection induced unique transcriptional responses in human AMs compared with MDMs, including upregulation of the IFN response pathway and specific DNA sensors.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246756","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

Cutting Edge: ATP13A2 Is an Endolysosomal Regulator of TLR9/7 Activation in Human Plasmacytoid Dendritic Cells. 前沿：ATP13A2 是人类浆细胞树突状细胞中 TLR9/7 激活的溶酶体内调节器。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-07-15 DOI: 10.4049/jimmunol.2300733

Purbita Bandopadhyay, Jafar Sarif, Ranit D'Rozario, Chinky Shiu Chen Liu, Bishnu P Sinha, Md Asmaul Hoque, Koustav Chatterjee, Supriyo Choudhury, Hrishikesh Kumar, Deblina Raychaudhuri, Dipyaman Ganguly

{"title":"Cutting Edge: ATP13A2 Is an Endolysosomal Regulator of TLR9/7 Activation in Human Plasmacytoid Dendritic Cells.","authors":"Purbita Bandopadhyay, Jafar Sarif, Ranit D'Rozario, Chinky Shiu Chen Liu, Bishnu P Sinha, Md Asmaul Hoque, Koustav Chatterjee, Supriyo Choudhury, Hrishikesh Kumar, Deblina Raychaudhuri, Dipyaman Ganguly","doi":"10.4049/jimmunol.2300733","DOIUrl":"10.4049/jimmunol.2300733","url":null,"abstract":"ATPase cation transporting 13A2 (ATP13A2) is an endolysosomal P-type ATPase known to be a polyamine transporter, explored mostly in neurons. As endolysosomal functions are also crucial in innate immune cells, we aimed to explore the potential role of ATP13A2 in the human immunocellular compartment. We found that human plasmacytoid dendritic cells (pDCs), the professional type I IFN-producing immune cells, especially have a prominent enrichment of ATP13A2 expression in endolysosomal compartments. ATP13A2 knockdown in human pDCs interferes with cytokine induction in response to TLR9/7 activation in response to bona fide ligands. ATP13A2 plays this crucial role in TLR9/7 activation in human pDCs by regulating endolysosomal pH and mitochondrial reactive oxygen generation. This (to our knowledge) hitherto unknown regulatory mechanism in pDCs involving ATP13A2 opens up a new avenue of research, given the crucial role of pDC-derived type I IFNs in protective immunity against infections as well as in the immunopathogenesis of myriad contexts of autoreactive inflammation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476743","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

Diminished γδ T Cells during Murine Allergic Skin Inflammation Is Mediated by IL-4 Signaling in Keratinocytes. 小鼠过敏性皮肤炎症期间γδ T 细胞的减少是由角质形成细胞中的 IL-4 信号介导的

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-07-15 DOI: 10.4049/jimmunol.2300629

Wenwu Zhang, Abigail Pajulas, Michelle Niese, Hongming Zhou, Jennifer Zhao, Nahid Akhtar, Matthew J Turner, Mark H Kaplan

{"title":"Diminished γδ T Cells during Murine Allergic Skin Inflammation Is Mediated by IL-4 Signaling in Keratinocytes.","authors":"Wenwu Zhang, Abigail Pajulas, Michelle Niese, Hongming Zhou, Jennifer Zhao, Nahid Akhtar, Matthew J Turner, Mark H Kaplan","doi":"10.4049/jimmunol.2300629","DOIUrl":"10.4049/jimmunol.2300629","url":null,"abstract":"Atopic dermatitis results in diminished barrier function and altered production of antimicrobial peptides. Dendritic epidermal T cells (DETCs) play an important role in the wound repair and inflammation process. Our previous work identified an IL-4-dependent loss of DETCs in Stat6VT mice and in the MC903-induced skin inflammation mouse model. However, the mechanisms through which IL-4 mediates the loss of DETCs are unclear. In this study, we show that IL-4Rα germline knockout mice (Il4ra-/-) have increased DETCs, faster wound healing, and increased epidermal differentiation complex gene and fibronectin expression. The absence of IL-4Rα minimized the MC903-induced loss of DETCs, and reciprocal bone marrow chimera experiments in Il4ra-/- and wild-type mice demonstrated structural nonhematopoietic IL-4-responsive cell-mediated DETC homeostasis. Skin keratinocyte-derived IL-15 decreased dramatically in the MC903 model, while injection of IL-15 rescued DETC loss by promoting DETC proliferation and limiting apoptosis. Conditional deletion of IL-4Rα from keratinocytes using Il4rafl/fl K14-Cre mice showed an increase of DETCs, increased IL-15 production, and diminished skin inflammation following wounding. These results suggest that IL-4-dependent effects on DETCs in allergic skin inflammation are mediated by the IL-4Rα receptor of keratinocytes.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088115","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

SKI Regulates Medullary Thymic Epithelial Cell Differentiation to Control Peripheral T Cell Responses in Mice. SKI 调控小鼠髓质胸腺上皮细胞分化以控制外周 T 细胞反应

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-07-01 DOI: 10.4049/jimmunol.2300262

Honyin Chiu, Kristin N Weinstein, Sabine Spath, Alex Hu, Stephanie Varela, Kazushige Obata-Ninomiya, Steven F Ziegler

{"title":"SKI Regulates Medullary Thymic Epithelial Cell Differentiation to Control Peripheral T Cell Responses in Mice.","authors":"Honyin Chiu, Kristin N Weinstein, Sabine Spath, Alex Hu, Stephanie Varela, Kazushige Obata-Ninomiya, Steven F Ziegler","doi":"10.4049/jimmunol.2300262","DOIUrl":"10.4049/jimmunol.2300262","url":null,"abstract":"The thymus is an important site for the establishment of an appropriate immune response through positive and negative selection of developing T cells. During selection, developing T cells interact with cortical and medullary thymic epithelial cells (TECs), termed cTECs and mTECs, respectively. Using a Foxn1Cre+/-SKIfl/fl mouse model, we found that TEC-specific deletion of SKI reduced the mTEC compartment in the thymus and that tissue-restricted Ag expression in mTECs was altered. This decrease in the medullary area led to a decrease in CD4 thymocyte cellularity; however, mature CD4 cellularity in the spleen remained normal. Interestingly, naive CD4 T cells purified from SKI-deleted mice showed a defect in proliferation in vitro after global TCR stimulation, and these mice were significantly protected from developing experimental autoimmune encephalomyelitis compared with the control mice. Overall, our findings suggest that SKI signaling in the thymus regulates mTEC differentiation and function as well as downstream peripheral T cell responses and provide evidence for targeting SKI in T cell-driven autoimmune diseases such as multiple sclerosis.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065619","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