Journal of immunology最新文献

Ubiquitination of Hemocyanin Mediated by a Mitochondrial E3 Ubiquitin Ligase Regulates Immune Response in Penaeus vannamei. 线粒体 E3 泛素连接酶介导的血蓝蛋白泛素化调节凡纳滨对虾的免疫反应

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-08 DOI: 10.4049/jimmunol.2400493

Xiaojun Zhang, Zhaoxue Zhang, Zhihong Zheng, Defu Yao, Yongzhen Zhao, Qingyun Liu, Zhongyang Lin, Yueling Zhang

{"title":"Ubiquitination of Hemocyanin Mediated by a Mitochondrial E3 Ubiquitin Ligase Regulates Immune Response in Penaeus vannamei.","authors":"Xiaojun Zhang, Zhaoxue Zhang, Zhihong Zheng, Defu Yao, Yongzhen Zhao, Qingyun Liu, Zhongyang Lin, Yueling Zhang","doi":"10.4049/jimmunol.2400493","DOIUrl":"https://doi.org/10.4049/jimmunol.2400493","url":null,"abstract":"Ubiquitination is a critical posttranslational modification that regulates host immune responses to pathogens. In this study, we investigated the ubiquitination of hemocyanin (PvHMC [Penaeus vannamei hemocyanin]) mediated by the mitochondrial E3 ubiquitin ligase (PvMulan) in shrimp Penaeus vannamei. We characterized distinct ubiquitination patterns of PvHMC in response to different pathogen challenges, both in vitro and in vivo. Specifically, we found that Vibrio parahaemolyticus infection led to an increase in PvMulan, which resulted in K48-linked ubiquitination and subsequent proteasomal degradation of PvHMC. In contrast, PvMulan primarily enhanced the SUMOylation of PvHMC, bolstering its immune functions against white spot syndrome virus challenges. Inhibition of PvMulan-mediated PvHMC ubiquitination significantly affected the proliferation of V. parahaemolyticus and the survival rate of infected shrimps. This study sheds light on the role of hemocyanin ubiquitination in immune regulation, illustrating its dual function in response to distinct pathogens.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604979","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

Diverse Epithelial Lymphocytes in Zebrafish Revealed Using a Novel Scale Biopsy Method. 利用新型鳞片活检法揭示斑马鱼上皮淋巴细胞的多样性

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-06 DOI: 10.4049/jimmunol.2300818

Gilseung Park, Clay A Foster, Megan Malone-Perez, Ameera Hasan, Jose Juan Macias, J Kimble Frazer

{"title":"Diverse Epithelial Lymphocytes in Zebrafish Revealed Using a Novel Scale Biopsy Method.","authors":"Gilseung Park, Clay A Foster, Megan Malone-Perez, Ameera Hasan, Jose Juan Macias, J Kimble Frazer","doi":"10.4049/jimmunol.2300818","DOIUrl":"10.4049/jimmunol.2300818","url":null,"abstract":"Zebrafish (Danio rerio) are a compelling model for studying lymphocytes because zebrafish and humans have similar adaptive immune systems, including their lymphocytes. Antibodies that recognize zebrafish proteins are sparse, so many investigators use transgenic, lymphocyte-specific fluorophore-labeled lines. Human and zebrafish lymphocyte types are conserved, but many aspects of zebrafish lymphocyte biology remain uninvestigated, including lymphocytes in peripheral tissues, like epidermis. This study is, to our knowledge, the first study to focus on zebrafish epidermal lymphocytes, using scales. Obtaining zebrafish blood via nonlethal methods is difficult; scales represent a source to longitudinally sample live fish. We developed a novel biopsy technique, collecting scales to analyze epithelial lymphocytes from several transgenic lines. We imaged scales via confocal microscopy and demonstrated multiple lymphocyte types in scales/epidermis, quantifying them flow cytometrically. We profiled gene expression of scale, thymic, and kidney-marrow (analogous to mammalian bone marrow) lymphocytes from the same animals, revealing B- and T-lineage signatures. Single-cell quantitative real-time PCR and RNA sequencing show not only canonical B and T cells but also novel lymphocyte populations not described previously. To validate longitudinal scale biopsies, we serially sampled scales from fish treated with dexamethasone, demonstrating epidermal lymphocyte responses. To analyze cells functionally, we employed a bead-ingestion assay, showing that thymic, marrow, and epidermal lymphocytes have phagocytic activity. In summary, we establish a novel, nonlethal technique to obtain zebrafish lymphocytes, providing the first quantification, expression profiling, and functional data from zebrafish epidermal lymphocytes.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583485","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: Subclinical Herpes Simplex Virus Type 1 Infections Provide Site-Specific Resistance to an Unrelated Pathogen. 更正：亚临床 1 型单纯疱疹病毒感染会对一种无关的病原体产生特定部位的抵抗力。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-06 DOI: 10.4049/jimmunol.2400607

Alexander M Rowe, Hongmin Yun, Benjamin R Treat, Paul R Kinchington, Robert L Hendricks

引用次数: 0

The HMGBa-HSP70-ATF4-β Axis Restricts White Spot Syndrome Virus Infection in Crayfish. HMGBa-HSP70-ATF4-β轴限制螯虾感染白斑综合征病毒

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-04 DOI: 10.4049/jimmunol.2400425

Xiao-Tong Cao, Yan Liu, Jie-Jie Sun, Shi-Jin Jiang, Jiang-Feng Lan

{"title":"The HMGBa-HSP70-ATF4-β Axis Restricts White Spot Syndrome Virus Infection in Crayfish.","authors":"Xiao-Tong Cao, Yan Liu, Jie-Jie Sun, Shi-Jin Jiang, Jiang-Feng Lan","doi":"10.4049/jimmunol.2400425","DOIUrl":"https://doi.org/10.4049/jimmunol.2400425","url":null,"abstract":"Envelope viruses are the most threatening pathogens to eukaryotes. The search for target genes against envelope viruses is particularly important. The activating transcription factors (ATFs) regulate cancer proliferation, maintain cellular redox homeostasis, extend biological longevity, and respond to viral stimuli. However, the mechanism of ATF antiviral immunity, especially envelope viruses, is rarely reported. Two ATF4 homologs (ATF4-α and ATF4-β) with a difference of one β sheet (7 amino acids) were identified in crayfish. Further studies showed that ATF4-β was activated and significantly translocated into the nucleus after envelope virus white spot syndrome virus (WSSV) infection. During WSSV infection, the host may recognize WSSV in some way (such as HMGBa recognizing WSSV by interacting with WSSV/VP28) and transmits the signal to cell, and then HMGBa, HSP70, and ATF4-β interact with each other in the cytoplasm and promote nuclear translocation of ATF4-β. ATF4-β entered the nucleus to initiate the transcription of ATF4 and ALFs. In addition, ALF1 could bind to VP28 to inhibit virus assembly in the nucleus and reinfection. This study elucidated a novel mechanism of ATF4-β in antienvelope virus immune responses, and ATF4 may be a potential target for disease prevention and control.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568207","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

ISG15 Drives Immune Pathology and Respiratory Failure during Systemic Lymphocytic Choriomeningitis Virus Infection. ISG15驱动全身淋巴细胞性脉络膜炎病毒感染期间的免疫病理学和呼吸衰竭

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-04 DOI: 10.4049/jimmunol.2400042

Namir Shaabani, Jaroslav Zak, Jennifer L Johnson, Zhe Huang, Nhan Nguyen, Daniel C Lazar, Vincent F Vartabedian, Nadine Honke, Joseph G Jardine, Jordan Woehl, Marco Prinz, Klaus-Peter Knobeloch, Kei-Ichiro Arimoto, Dong-Er Zhang, Sergio D Catz, John R Teijaro

{"title":"ISG15 Drives Immune Pathology and Respiratory Failure during Systemic Lymphocytic Choriomeningitis Virus Infection.","authors":"Namir Shaabani, Jaroslav Zak, Jennifer L Johnson, Zhe Huang, Nhan Nguyen, Daniel C Lazar, Vincent F Vartabedian, Nadine Honke, Joseph G Jardine, Jordan Woehl, Marco Prinz, Klaus-Peter Knobeloch, Kei-Ichiro Arimoto, Dong-Er Zhang, Sergio D Catz, John R Teijaro","doi":"10.4049/jimmunol.2400042","DOIUrl":"https://doi.org/10.4049/jimmunol.2400042","url":null,"abstract":"ISG15, an IFN-stimulated gene, plays a crucial role in modulating immune responses during viral infections. Its upregulation is part of the host's defense mechanism against viruses, contributing to the antiviral state of cells. However, altered ISG15 expression can also lead to immune dysregulation and pathological outcomes, particularly during persistent viral infections. Understanding the balance of ISG15 in promoting antiviral immunity while avoiding immune-mediated pathology is essential for developing targeted therapeutic interventions against viral diseases. In this article, using Usp18-deficient, USP18 enzymatic-inactive and Isg15-deficient mouse models, we report that a lack of USP18 enzymatic function during persistent viral infection leads to severe immune pathology characterized by hematological disruptions described by reductions in platelets, total WBCs, and lymphocyte counts; pulmonary cytokine amplification; lung vascular leakage; and death. The lack of Usp18 in myeloid cells mimicked the pathological manifestations observed in Usp18-/- mice and required Isg15. Mechanistically, interrupting the enzymes that conjugate/deconjugate ISG15, using Uba7-/- or Usp18C61A mice, respectively, led to accumulation of ISG15 that was accompanied by inflammatory neutrophil accumulation, lung pathology, and death similar to that observed in Usp18-deficient mice. Moreover, myeloid cell depletion reversed pathological manifestations, morbidity, and mortality in Usp18C61A mice. Our results suggest that dysregulated ISG15 production and signaling during persistent lymphocytic choriomeningitis virus infection can produce lethal immune pathology and could serve as a therapeutic target during severe viral infections with pulmonary pathological manifestations.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568219","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

IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation. IL-1β 通过缓解 let-7c-3p 对蛋白质翻译的抑制，诱导人内皮细胞表面表达 IL-15。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-01 DOI: 10.4049/jimmunol.2400331

Clancy W Mullan, Luanna Summer, Francesc Lopez-Giraldez, Zuzana Tobiasova, Thomas D Manes, Shruthi Yasothan, Guiyu Song, Daniel Jane-Wit, W Mark Saltzman, Jordan S Pober

{"title":"IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation.","authors":"Clancy W Mullan, Luanna Summer, Francesc Lopez-Giraldez, Zuzana Tobiasova, Thomas D Manes, Shruthi Yasothan, Guiyu Song, Daniel Jane-Wit, W Mark Saltzman, Jordan S Pober","doi":"10.4049/jimmunol.2400331","DOIUrl":"10.4049/jimmunol.2400331","url":null,"abstract":"Expression of IL-15 on the surface of human graft endothelial cells (ECs) bound to the IL-15Rα subunit can increase the activation of CTLs, potentiating allograft rejection. Our previous work showed that surface expression of this protein complex could be induced by alloantibody-mediated complement activation through increased IL-1β synthesis, secretion, and autocrine/paracrine IL-1-mediated activation of NF-κB. In this article, we report that cultured human ECs express eight differently spliced IL-15 transcripts. Remarkably, IL-1β does not alter the expression level of any IL-15 transcript but induces surface expression independently of RNA polymerase II-mediated transcription while requiring new protein translation. Mechanistically, IL-1β causes an NF-κB-mediated reduction in the level of microRNA Let-7c-3p, thereby relieving a block of translation of IL-15 surface protein. Let7c-3p anti-miR can induce EC surface expression of IL-15/IL-15Rα in the absence of complement activation or of IL-1, enabling IL-15 transpresentation to boost CD8 T cell activation. Because of the complexity we have uncovered in IL-15 regulation, we recommend caution in interpreting increased total IL-15 mRNA or protein levels as a surrogate for transpresentation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289200","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 G Protein-Coupled Receptor GPR56 Is an Inhibitory Checkpoint for NK Cell Migration. G 蛋白偶联受体 GPR56 是 NK 细胞迁移的抑制性检查点

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-01 DOI: 10.4049/jimmunol.2400228

Daniel Palacios, Rakesh Kumar Majhi, Edina K Szabo, Dennis Clement, Mieszko Lachota, Herman Netskar, Leena Penna, Silje Z Krokeide, Marianna Vincenti, Lise Kveberg, Karl-Johan Malmberg

{"title":"The G Protein-Coupled Receptor GPR56 Is an Inhibitory Checkpoint for NK Cell Migration.","authors":"Daniel Palacios, Rakesh Kumar Majhi, Edina K Szabo, Dennis Clement, Mieszko Lachota, Herman Netskar, Leena Penna, Silje Z Krokeide, Marianna Vincenti, Lise Kveberg, Karl-Johan Malmberg","doi":"10.4049/jimmunol.2400228","DOIUrl":"10.4049/jimmunol.2400228","url":null,"abstract":"G protein-coupled receptors (GPCRs) represent the largest family of surface receptors and are responsible for key physiological functions, including cell growth, neurotransmission, hormone release, and cell migration. The GPCR 56 (GPR56), encoded by ADGRG1, is an adhesion GPCR found on diverse cell types, including neural progenitor cells, melanoma cells, and lymphocytes, such as effector memory T cells, γδ T cells, and NK cells. Using RNA-sequencing and high-resolution flow cytometry, we found that GPR56 mRNA and protein expression increased with NK cell differentiation, reaching its peak in adaptive NK cells. Small interfering RNA silencing of GPR56 led to increased spontaneous and chemokine-induced migration, suggesting that GPR56 functions as an upstream checkpoint for migration of highly differentiated NK cells. Increased NK cell migration could also be induced by agonistic stimulation of GPR56 leading to rapid internalization and deactivation of the receptor. Mechanistically, GPR56 ligation and downregulation were associated with transcriptional coactivator with PDZ-binding motif translocation to the nucleus and increased actin polymerization. Together, these data provide insights into the role of GPR56 in the migratory behavior of human NK cell subsets and may open possibilities to improve NK cell infiltration into cancer tissues by releasing a migratory checkpoint.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348206","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

Nrf2 Regulates Inflammation by Modulating Dendritic Cell-T Cell Crosstalk during Viral-Bacterial Superinfection. Nrf2通过调节病毒-细菌超级感染过程中树突状细胞-T细胞的串联调节炎症

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-01 DOI: 10.4049/jimmunol.2400322

Alexis M Duray, Leigh M Miller, Brooke P Dresden, Flavia Rago, Danielle Antos, Kevin J McHugh, John F Alcorn

{"title":"Nrf2 Regulates Inflammation by Modulating Dendritic Cell-T Cell Crosstalk during Viral-Bacterial Superinfection.","authors":"Alexis M Duray, Leigh M Miller, Brooke P Dresden, Flavia Rago, Danielle Antos, Kevin J McHugh, John F Alcorn","doi":"10.4049/jimmunol.2400322","DOIUrl":"https://doi.org/10.4049/jimmunol.2400322","url":null,"abstract":"Every year millions of people are infected with influenza, which can be complicated by secondary bacterial pneumonia. One factor that may contribute to increased susceptibility to secondary bacterial infection is the modulation of inflammatory cytokines. NF erythroid 2-related factor 2 (Nrf2) has been shown to be a master regulator of the antioxidant response and various inflammatory cytokines. To test the role of Nrf2 during viral-bacterial superinfection, we used a mouse model of influenza-Staphylococcus aureus superinfection with wild-type (WT) or Nrf2-deficient (Nrf2-/-) mice. Loss of Nrf2 reduced influenza burden and increased S. aureus burden during superinfection. Additionally, Nrf2-/- mice had increased abundance of conventional type 1 dendritic cells (DCs). We then tested the interaction between DCs and T cells using an in vitro model of bone marrow-derived DCs with OVA and OT-II T cells. In this system, Nrf2-/- DCs promoted a Th2/regulatory T cell response as opposed to a Th1/Th17 response by WT DCs. This was recapitulated in vivo with superinfected Nrf2-/- mice having increased regulatory T cell populations. We also observed an increased median survival time of Nrf2-/- superinfected mice, due at least in part to increased IL-10 signaling, as anti-IL-10R Ab treatment reduced median survival time to levels seen in WT mice. Overall, these data suggest that loss of Nrf2 promotes differential T cell skewing mediated by DCs that promote a regulatory phenotype, increasing superinfection survival time, despite increased bacterial burden.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558052","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

Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis. 几丁质酶 3-like-1 通过调节 CD47-SIRPα 和 CD24-Siglec10 介导的吞噬作用抑制先天性抗肿瘤和组织重塑免疫反应

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-01 DOI: 10.4049/jimmunol.2400035

Bing Ma, Suchitra Kamle, Takayuki Sadanaga, Chang-Min Lee, Joyce H Lee, Daniel C Yee, Zhou Zhu, Edwin K Silverman, Dawn L DeMeo, Augustine M K Choi, Chun Geun Lee, Jack A Elias

{"title":"Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis.","authors":"Bing Ma, Suchitra Kamle, Takayuki Sadanaga, Chang-Min Lee, Joyce H Lee, Daniel C Yee, Zhou Zhu, Edwin K Silverman, Dawn L DeMeo, Augustine M K Choi, Chun Geun Lee, Jack A Elias","doi":"10.4049/jimmunol.2400035","DOIUrl":"10.4049/jimmunol.2400035","url":null,"abstract":"Innate immune responses such as phagocytosis are critically linked to the generation of adaptive immune responses against the neoantigens in cancer and the efferocytosis that is essential for homeostasis in diseases characterized by lung injury, inflammation, and remodeling as in chronic obstructive pulmonary disease (COPD). Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it inhibits adaptive immune responses by stimulating immune checkpoint molecules (ICPs) and portends a poor prognosis. CHI3L1 is also induced in COPD where it regulates epithelial cell death. In this study, we demonstrate that pulmonary melanoma metastasis inhibits macrophage phagocytosis by stimulating the CD47-SIRPα and CD24-Siglec10 phagocytosis checkpoint pathways while inhibiting macrophage \"eat me\" signals from calreticulin and HMGB1. We also demonstrate that these effects on macrophage phagocytosis are associated with CHI3L1 stimulation of the SHP-1 and SHP-2 phosphatases and inhibition of the accumulation and phosphorylation of cytoskeleton-regulating nonmuscle myosin IIa. This inhibition of innate immune responses such as phagocytosis provides a mechanistic explanation for the ability of CHI3L1 to stimulate ICPs and inhibit adaptive immune responses in cancer and diseases such as COPD. The ability of CHI3L1 to simultaneously inhibit innate immune responses, stimulate ICPs, inhibit T cell costimulation, and regulate a number of other oncogenic and inflammation pathways suggests that CHI3L1-targeted therapeutics are promising interventions in cancer, COPD, and other disorders.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289197","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

Type I IFN Induces TCR-dependent and -independent Antimicrobial Responses in γδ Intraepithelial Lymphocytes. I 型 IFN 在γδ上皮内淋巴细胞中诱导依赖和不依赖 TCR 的抗微生物反应。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-11-01 DOI: 10.4049/jimmunol.2400138

Matthew A Fischer, Luo Jia, Karen L Edelblum

{"title":"Type I IFN Induces TCR-dependent and -independent Antimicrobial Responses in γδ Intraepithelial Lymphocytes.","authors":"Matthew A Fischer, Luo Jia, Karen L Edelblum","doi":"10.4049/jimmunol.2400138","DOIUrl":"10.4049/jimmunol.2400138","url":null,"abstract":"Intraepithelial lymphocytes (IELs) expressing the TCRγδ survey the intestinal epithelium to limit the invasion of microbial pathogens. The production of type I IFN is a central component of an antiviral immune response, yet how these proinflammatory cytokines contribute to γδ IEL effector function remains unclear. Based on the unique activation status of IELs and their ability to bridge innate and adaptive immunity, we investigated the extent to which type I IFN signaling modulates γδ IEL function. Using an ex vivo culture model, we find that type I IFN alone is unable to drive IFN-γ production, yet low-level TCR activation synergizes with type I IFN to induce IFN-γ production in murine γδ IELs. Further investigation into the underlying molecular mechanisms of costimulation revealed that TCRγδ-mediated activation of NFAT and JNK is required for type I IFN to promote IFN-γ expression in a STAT4-dependent manner. Whereas type I IFN rapidly upregulates antiviral gene expression independent of a basal TCRγδ signal, neither tonic TCR triggering nor the presence of a TCR agonist was sufficient to elicit type I IFN-induced IFN-γ production in vivo. However, bypassing proximal TCR signaling events synergized with IFNAR/STAT4 activation to induce γδ IEL IFN-γ production. These findings indicate that γδ IELs contribute to host defense in response to type I IFN by mounting a rapid antimicrobial response independent of TCRγδ signaling, and may produce IFN-γ in a TCR-dependent manner under permissive conditions.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289205","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