ImmunoHorizons最新文献

{"title":"B-1a Cells, but Not Marginal Zone B Cells, Are Implicated in the Accumulation of Autoreactive Plasma Cells in Lyn-/- Mice.","authors":"Kristina Ottens, Jalyn Schneider, Anne B Satterthwaite","doi":"10.4049/immunohorizons.2300089","DOIUrl":"10.4049/immunohorizons.2300089","url":null,"abstract":"<p><p>Mice deficient in Lyn, a tyrosine kinase that limits B cell activation, develop a lupus-like autoimmune disease characterized by the accumulation of splenic plasma cells and the production of autoantibodies. Lyn-/- mice have reduced numbers of marginal zone (MZ) B cells, a B cell subset that is enriched in autoreactivity and prone to plasma cell differentiation. We hypothesized that this is due to unchecked terminal differentiation of this potentially pathogenic B cell subpopulation. However, impairing MZ B cell development in Lyn-/- mice did not reduce plasma cell accumulation or autoantibodies, and preventing plasma cell differentiation did not restore MZ B cell numbers. Instead, Lyn-/- mice accumulated B-1a cells when plasma cell differentiation was impaired. Similar to MZ B cells, B-1a cells tend to be polyreactive or weakly autoreactive and are primed for terminal differentiation. Our results implicate B-1a cells, but not MZ B cells, as contributors to the autoreactive plasma cell pool in Lyn-/- mice.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"47-56"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LNCGM1082 in Gut Epithelial Cells Promotes Expulsion of Infected Epithelial Cells and Release of IL-18.","authors":"Ya Wang, Yunhuan Gao, Xiaomin Su, Yang Hao, Yuan Zhang, Rongcun Yang","doi":"10.4049/immunohorizons.2300110","DOIUrl":"10.4049/immunohorizons.2300110","url":null,"abstract":"<p><p>Inflammasome NLRC4 (NLR family CARD domain containing 4) can protect mucosal barriers such as intestine from invading bacterial pathogens. However, it was incompletely clear how NLRC4 was activated in intestinal epithelial cells. In this study, we demonstrated that LNCGM1082 could mediate the activation of NLRC4 via binding NLRC4 with protein kinase C (PKC)δ. LNCGM1082 knockout (KO) mice had reduced resistance against Salmonella Typhimurium infection, as well as impaired expulsion of infected gut epithelial cells and release of IL-18 upon exposure to S. Typhimurium. Similar to NLRC4 KO and PKCδ knockdown gut organoids, there also was impaired expulsion of gut epithelial cells and release of IL-18 in LNCGM1082 KO gut organoids. Furthermore, there also was reduced activation of caspase-1 and caspase-8 in these LNCGM1082 KO, NLRC4 KO, and PKCδ knockdown gut organoids upon exposure to S. Typhimurium. Our results show that LNCGM1082 in the ICEs plays a critical role in mediating activation of NLRC4 through binding NLRC4 and PKCδ and promoting expulsion of infected epithelial cells and release of IL-18 upon exposure to bacteria such as S. Typhimurium.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"35-46"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CTLA-4 Checkpoint Inhibition Improves Sepsis Survival in Alcohol-Exposed Mice.","authors":"Cameron W Paterson, Katherine T Fay, Ching-Wen Chen, Nathan J Klingensmith, Melissa B Gutierrez, Zhe Liang, Craig M Coopersmith, Mandy L Ford","doi":"10.4049/immunohorizons.2300060","DOIUrl":"10.4049/immunohorizons.2300060","url":null,"abstract":"<p><p>Chronic alcohol use increases morbidity and mortality in the setting of sepsis. Both chronic alcohol use and sepsis are characterized by immune dysregulation, including overexpression of T cell coinhibitory molecules. We sought to characterize the role of CTLA-4 during sepsis in the setting of chronic alcohol exposure using a murine model of chronic alcohol ingestion followed by cecal ligation and puncture. Results indicated that CTLA-4 expression is increased on CD4+ T cells isolated from alcohol-drinking septic mice as compared with either alcohol-drinking sham controls or water-drinking septic mice. Moreover, checkpoint inhibition of CTLA-4 improved sepsis survival in alcohol-drinking septic mice, but not water-drinking septic mice. Interrogation of the T cell compartments in these animals following pharmacologic CTLA-4 blockade, as well as following conditional Ctla4 deletion in CD4+ T cells, revealed that CTLA-4 deficiency promoted the activation and proliferation of effector regulatory T cells and the generation of conventional effector memory CD4+ T cells. These data highlight an important role for CTLA-4 in mediating mortality during sepsis in the setting of chronic alcohol exposure and may inform future approaches to develop targeted therapies for this patient population.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"74-88"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139473040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the Effectiveness of Team-based Learning Activities on Learning Outcomes in the Undergraduate Immunology Classroom.","authors":"Joshua J Baty, Heather A Bruns","doi":"10.4049/immunohorizons.2300073","DOIUrl":"10.4049/immunohorizons.2300073","url":null,"abstract":"<p><p>Immunology is inherently interdisciplinary. Understanding how the immune system functions requires knowledge from several scientific disciplines, including molecular biology, cellular biology, genetics, and biochemistry. Furthermore, immunology is conceptually complex, requiring the identification of a plethora of immune components and mastery of a large volume of new vocabulary. These attributes can pose challenges to student learning in the undergraduate immunology classroom. Team-based learning (TBL) is a pedagogical method used to increase student engagement in learning, improve student collaboration, and develop communication skills. In a variety of educational settings, TBL activities have been shown to foster a deeper understanding of complex topics, increase student confidence in course content, and improve learning outcomes. In this study, we examined differences in the impact of traditional lecture versus TBL activities on student learning outcomes for four different topics presented in an undergraduate adaptive immunity course composed largely of academically high-performing students. We matched content across two student cohorts, delivered via team-based learning methodology (T cell development and Ab-mediated functions) and traditional lecture (B cell development and T cell effector functions). Student learning was assessed using content questions across a range of Bloom's taxonomy levels, which demonstrated that the TBL activities did not improve examination performance over lecture-based learning in this course. However, students found this learning tool to be valuable, indicating that the TBL activities assisted with preparation for examinations and provided a necessary opportunity to address misconceptions.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"106-113"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody Response to the Sneathia vaginalis Cytopathogenic Toxin A during Pregnancy.","authors":"Zion T McCoy, Myrna G Serrano, Laahirie Edupuganti, Katherine M Spaine, David J Edwards, Gregory A Buck, Kimberly K Jefferson","doi":"10.4049/immunohorizons.2400001","DOIUrl":"10.4049/immunohorizons.2400001","url":null,"abstract":"<p><p>Sneathia vaginalis is a Gram-negative vaginal species that is associated with pregnancy complications. It produces cytopathogenic toxin A (CptA), a pore-forming toxin. To determine whether CptA is expressed in vivo and to examine the mucosal Ab response to the toxin, we examined human midvaginal swab samples obtained during pregnancy for IgM, IgA, and IgG Abs with CptA affinity. This subcohort study included samples from 93 pregnant people. S. vaginalis relative abundance was available through 16S rRNA survey. There were 22 samples from pregnancies that resulted in preterm birth in which S. vaginalis relative abundance was <0.005%, 22 samples from pregnancies that resulted in preterm birth with S. vaginalis ≥0.005%, 24 samples from pregnancies that resulted in term birth with S. vaginalis <0.005%, and 25 samples from pregnancies that resulted in term birth with S. vaginalis ≥0.005%. IgM, IgA, and IgG with affinity for CptA were assessed by ELISA. The capacity for the samples to neutralize CptA was quantified by hemolysis assay. All three Ab isotypes were detectable within different subsets of the samples. There was no significant association between relative abundance of S. vaginalis and the presence of any Ab isotype. The majority of vaginal swab samples containing detectable levels of anti-CptA Abs neutralized the hemolytic activity of CptA, with the strongest correlation between IgA and neutralizing activity. These results demonstrate that S. vaginalis produces CptA in vivo and that CptA is recognized by the host immune defenses, resulting in the production of Abs with toxin-neutralizing ability.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"114-121"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139565300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Role of MAVS Signaling for Murine Lipopolysaccharide-Induced Acute Kidney Injury.","authors":"Trang Anh Thi Tran, Yasunori Iwata, Linh Thuy Hoang, Shinji Kitajima, Shiori Yoneda-Nakagawa, Megumi Oshima, Norihiko Sakai, Tadashi Toyama, Yuta Yamamura, Hiroka Yamazaki, Akinori Hara, Miho Shimizu, Keisuke Sako, Taichiro Minami, Takahiro Yuasa, Keisuke Horikoshi, Daiki Hayashi, Sho Kajikawa, Takashi Wada","doi":"10.4049/immunohorizons.2300069","DOIUrl":"10.4049/immunohorizons.2300069","url":null,"abstract":"<p><p>Despite treatment advances, acute kidney injury (AKI)-related mortality rates are still high in hospitalized adults, often due to sepsis. Sepsis and AKI could synergistically worsen the outcomes of critically ill patients. TLR4 signaling and mitochondrial antiviral signaling protein (MAVS) signaling are innate immune responses essential in kidney diseases, but their involvement in sepsis-associated AKI (SA-AKI) remains unclear. We studied the role of MAVS in kidney injury related to the TLR4 signaling pathway using a murine LPS-induced AKI model in wild-type and MAVS-knockout mice. We confirmed the importance of M1 macrophage in SA-AKI through in vivo assessment of inflammatory responses. The TLR4 signaling pathway was upregulated in activated bone marrow-derived macrophages, in which MAVS helped maintain the LPS-suppressed TLR4 mRNA level. MAVS regulated redox homeostasis via NADPH oxidase Nox2 and mitochondrial reverse electron transport in macrophages to alleviate the TLR4 signaling response to LPS. Hypoxia-inducible factor 1α (HIF-1α) and AP-1 were key regulators of TLR4 transcription and connected MAVS-dependent reactive oxygen species signaling with the TLR4 pathway. Inhibition of succinate dehydrogenase could partly reduce inflammation in LPS-treated bone marrow-derived macrophages without MAVS. These findings highlight the renoprotective role of MAVS in LPS-induced AKI by regulating reactive oxygen species generation-related genes and maintaining redox balance. Controlling redox homeostasis through MAVS signaling may be a promising therapy for SA-AKI.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidized Low-Density Lipoprotein Accumulation in Macrophages Impairs Lipopolysaccharide-Induced Activation of AKT2, ATP Citrate Lyase, Acetyl-Coenzyme A Production, and Inflammatory Gene H3K27 Acetylation.","authors":"Kenneth K Y Ting, Pei Yu, Mudia Iyayi, Riley Dow, Sharon J Hyduk, Eric Floro, Hisham Ibrahim, Saraf Karim, Chanele K Polenz, Daniel A Winer, Minna Woo, Jonathan Rocheleau, Jenny Jongstra-Bilen, Myron I Cybulsky","doi":"10.4049/immunohorizons.2300101","DOIUrl":"10.4049/immunohorizons.2300101","url":null,"abstract":"<p><p>The accumulation of lipid and the formation of macrophage foam cells is a hallmark of atherosclerosis, a chronic inflammatory disease. To better understand the role of macrophage lipid accumulation in inflammation during atherogenesis, we studied early molecular events that follow the accumulation of oxidized low-density lipoprotein (oxLDL) in cultured mouse macrophages. We previously showed that oxLDL accumulation downregulates the inflammatory response in conjunction with downregulation of late-phase glycolysis. In this study, we show that within hours after LPS stimulation, macrophages with accumulated oxLDL maintain early-phase glycolysis but selectively downregulate activation of AKT2, one of three AKT isoforms. The inhibition of AKT2 activation reduced LPS-induced ATP citrate lyase activation, acetyl-CoA production, and acetylation of histone 3 lysine 27 (H3K27ac) in certain inflammatory gene promoters. In contrast to oxLDL, multiple early LPS-induced signaling pathways were inhibited in macrophages with accumulated cholesterol, including TBK1, AKT1, AKT2, MAPK, and NF-κB, and early-phase glycolysis. The selective inhibition of LPS-induced AKT2 activation was dependent on the generation of mitochondrial oxygen radicals during the accumulation of oxLDL in macrophages prior to LPS stimulation. This is consistent with increased oxidative phosphorylation, fatty acid synthesis, and oxidation pathways found by comparative transcriptomic analyses of oxLDL-loaded versus control macrophages. Our study shows a functional connection between oxLDL accumulation, inactivation of AKT2, and the inhibition of certain inflammatory genes through epigenetic changes that occur soon after LPS stimulation, independent of early-phase glycolysis.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"57-73"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric Antigen Cytotoxic Receptors for In Vivo Engineering of Tumor-Targeting NK Cells.","authors":"Neha Diwanji, Daniel Getts, Yuxiao Wang","doi":"10.4049/immunohorizons.2300099","DOIUrl":"10.4049/immunohorizons.2300099","url":null,"abstract":"<p><p>Chimeric Ag receptor (CAR) NK cells are challenging to manufacture and fail to achieve consistent tumor infiltration and sustained cytolytic function in the tumor microenvironment. In vivo engineering of NK cells using mRNA-based CAR delivery may overcome these issues. In this study, we developed an in vivo programming method by designing CARs that leverage the biology of NK cell receptors for cell type-specific expression and function. These CARs were engineered by fusion of a tumor recognition domain with the natural cytotoxic receptor family including NKp30, NKp44, and NKp46. Our results demonstrated that these natural cytotoxic receptor-based CARs can engage endogenous signaling adaptors to effectively activate human NK cells for tumor lysis and cytokine production. Specifically, we discovered that stable expression of an NKp44-based CAR was contingent on the presence of the immune cell-specific signaling adaptor DAP12. This innovative strategy facilitates direct in situ programming of NK cells, enhancing safety and minimizing off-target effects in nontargeted, healthy tissues.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"97-105"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR4 Ligands in Typhoid Vi Polysaccharide Subunit Vaccines Contribute to Immunogenicity.","authors":"Kishore R Alugupalli","doi":"10.4049/immunohorizons.2300085","DOIUrl":"10.4049/immunohorizons.2300085","url":null,"abstract":"<p><p>Activation of B cells and T cells requires the engagement of costimulatory signaling pathways in addition to Ag receptor signaling for efficient immune responses. None of the typhoid Vi polysaccharide (ViPS) subunit vaccines contains adjuvants that could activate costimulatory signaling pathways, yet these vaccines are very immunogenic. I hypothesized that residual TLR ligands present in the ViPS preparation used for making typhoid subunit vaccines account for the robust immune response generated by these vaccines. I show the presence of endotoxin, a potent agonist of TLR4, in ViPS preparations and ViPS vaccines. Furthermore, I found that ViPS obtained from various sources induces the production of proinflammatory cytokines such as IL-6 from mouse peritoneal exudate cells. Unconjugated and tetanus toxoid-conjugated ViPS vaccines activate human and mouse TLR4. Mice deficient in TLR4 or the signaling adaptors MyD88 and Trif (Toll/IL-1R domain-containing adapter inducing IFN-β) are severely impaired in generating anti-ViPS responses to these vaccines. Elimination of the TLR4 agonist in ViPS preparation resulted in the loss of immunogenicity, and addition of lipid A, a known TLR4 agonist, restored the immunogenicity. These data highlight the importance of associated TLR ligands in the immunogenicity of ViPS subunit vaccines.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"29-34"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139099426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT1 Employs Myeloid Cell-Extrinsic Mechanisms to Regulate the Neutrophil Response and Provide Protection against Invasive Klebsiella pneumoniae Lung Infection.","authors":"Shekina Gonzalez-Ferrer, Hernán F Peñaloza, Rick van der Geest, Zeyu Xiong, Atish Gheware, Mohammadreza Tabary, Megan Kochin, Kathryn Dalton, Henry Zou, Dequan Lou, Karina Lockwood, Yingze Zhang, William G Bain, Rama K Mallampalli, Anuradha Ray, Prabir Ray, Daria Van Tyne, Kong Chen, Janet S Lee","doi":"10.4049/immunohorizons.2300104","DOIUrl":"10.4049/immunohorizons.2300104","url":null,"abstract":"<p><p>Klebsiella pneumoniae (KP) is an extracellular Gram-negative bacterium that causes infections in the lower respiratory and urinary tracts and the bloodstream. STAT1 is a master transcription factor that acts to maintain T cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found that STAT1 deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil recruitment in the lung preceding widespread bacterial dissemination and lung injury development. Yet, myeloid cell STAT1 was dispensable for control of KP proliferation and dissemination, because myeloid cell-specific STAT1-deficient (LysMCre/WT;Stat1fl/fl) mice showed bacterial burden in the lung, liver, and kidney similar to that of their wild-type littermates. Surprisingly, IL-17-producing CD4+ T cells infiltrated Stat1-/- murine lungs early during KP infection. The increase in Th17 cells in the lung was not due to preexisting immunity against KP and was consistent with circulating rather than tissue-resident CD4+ T cells. However, blocking global IL-17 signaling with anti-IL-17RC administration led to increased proliferation and dissemination of KP, suggesting that IL-17 provided by other innate immune cells is essential in defense against KP. Contrastingly, depletion of CD4+ T cells reduced Stat1-/- murine lung bacterial burden, indicating that early CD4+ T cell activation in the setting of global STAT1 deficiency is pathogenic. Altogether, our findings suggest that STAT1 employs myeloid cell-extrinsic mechanisms to regulate neutrophil responses and provides protection against invasive KP by restricting nonspecific CD4+ T cell activation and immunopathology in the lung.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"122-135"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}