Journal of immunology最新文献_第6页

Mycobacterium tuberculosis Utilizes Serine/Threonine Kinase PknF to Evade NLRP3 Inflammasome-driven Caspase-1 and RIPK3/Caspase-8 Activation in Murine Dendritic Cells. 结核分枝杆菌利用丝氨酸/苏氨酸激酶 PknF 回避小鼠树突状细胞中 NLRP3 炎症体驱动的 Caspase-1 和 RIPK3/Caspase-8 激活。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2300753

Shivangi Rastogi, Akshaya Ganesh, Volker Briken

{"title":"Mycobacterium tuberculosis Utilizes Serine/Threonine Kinase PknF to Evade NLRP3 Inflammasome-driven Caspase-1 and RIPK3/Caspase-8 Activation in Murine Dendritic Cells.","authors":"Shivangi Rastogi, Akshaya Ganesh, Volker Briken","doi":"10.4049/jimmunol.2300753","DOIUrl":"10.4049/jimmunol.2300753","url":null,"abstract":"Dendritic cells (DCs) are crucial for initiating the acquired immune response to infectious diseases such as tuberculosis. Mycobacterium tuberculosis has evolved strategies to inhibit activation of the NLRP3 inflammasome in macrophages via its serine/threonine protein kinase, protein kinase F (PknF). It is not known whether this pathway is conserved in DCs. In this study, we show that the pknF deletion mutant of M. tuberculosis (MtbΔpknF) compared with wild-type M. tuberculosis-infected cells induces increased production of IL-1β and increased pyroptosis in murine bone marrow-derived DCs (BMDCs). As shown for murine macrophages, the enhanced production of IL-1β postinfection of BMDCs with MtbΔpknF is dependent on NLRP3, ASC, and caspase-1/11. In contrast to macrophages, we show that MtbΔpknF mediates RIPK3/caspase-8-dependent IL-1β production in BMDCs. Consistently, infection with MtbΔpknF results in increased activation of caspase-1 and caspase-8 in BMDCs. When compared with M. tuberculosis-infected cells, the IL-6 production by MtbΔpknF-infected cells was unchanged, indicating that the mutant does not affect the priming phase of inflammasome activation. In contrast, the activation phase was impacted because the MtbΔpknF-induced inflammasome activation in BMDCs depended on potassium efflux, chloride efflux, reactive oxygen species generation, and calcium influx. In conclusion, PknF is important for M. tuberculosis to evade NLRP3 inflammasome-mediated activation of caspase-1 and RIPK3/caspase-8 pathways in BMDCs.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"690-699"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633692","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

IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10. IL-27基因疗法可改善Foxp3基因种系突变引起的IPEX综合征：IL-10的诱导起主要作用。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2400056

Jin-Qing Liu, Ali Jabbari, Cho-Hao Lin, Venu Akkanapally, Wendy L Frankel, Sujit Basu, Kai He, Pan Zheng, Yang Liu, Xue-Feng Bai

{"title":"IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10.","authors":"Jin-Qing Liu, Ali Jabbari, Cho-Hao Lin, Venu Akkanapally, Wendy L Frankel, Sujit Basu, Kai He, Pan Zheng, Yang Liu, Xue-Feng Bai","doi":"10.4049/jimmunol.2400056","DOIUrl":"10.4049/jimmunol.2400056","url":null,"abstract":"Inactivating mutations of Foxp3, the master regulator of regulatory T cell development and function, lead to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in mice and humans. IPEX is a fatal autoimmune disease, with allogeneic stem cell transplant being the only available therapy. In this study, we report that a single dose of adeno-associated virus (AAV)-IL-27 to young mice with naturally occurring Foxp3 mutation (Scurfy mice) substantially ameliorates clinical symptoms, including growth retardation and early fatality. Correspondingly, AAV-IL-27 gene therapy significantly prevented naive T cell activation, as manifested by downregulation of CD62L and upregulation of CD44, and immunopathology typical of IPEX. Because IL-27 is known to induce IL-10, a key effector molecule of regulatory T cells, we evaluated the contribution of IL-10 induction by crossing IL-10-null allele to Scurfy mice. Although IL-10 deficiency does not affect the survival of Scurfy mice, it largely abrogated the therapeutic effect of AAV-IL-27. Our study revealed a major role for IL-10 in AAV-IL-27 gene therapy and demonstrated that IPEX is amenable to gene therapy.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"559-566"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554964","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

TLR10 (CD290) Is a Regulator of Immune Responses in Human Plasmacytoid Dendritic Cells. TLR10（CD290）是人类浆细胞树突状细胞免疫反应的调节因子

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2200468

Pratik Deb, Sukhwinder Singh, Evelyne Kalyoussef, Nicholas J Hess, Richard I Tapping, Patricia Fitzgerald-Bocarsly

{"title":"TLR10 (CD290) Is a Regulator of Immune Responses in Human Plasmacytoid Dendritic Cells.","authors":"Pratik Deb, Sukhwinder Singh, Evelyne Kalyoussef, Nicholas J Hess, Richard I Tapping, Patricia Fitzgerald-Bocarsly","doi":"10.4049/jimmunol.2200468","DOIUrl":"10.4049/jimmunol.2200468","url":null,"abstract":"TLRs are the most thoroughly studied group of pattern-recognition receptors that play a central role in innate immunity. Among them, TLR10 (CD290) remains the only TLR family member without a known ligand and clearly defined functions. One major impediment to studying TLR10 is its absence in mice. A recent study on TLR10 knock-in mice demonstrated its intrinsic inhibitory role in B cells, indicating that TLR10 is a potential drug target in autoimmune diseases. In this study, we interrogated the expression and function of TLR10 in human plasmacytoid dendritic cells (pDCs). We have seen that primary human pDCs, B cells, and monocytes constitutively express TLR10. Upon preincubation with an anti-TLR10 Ab, production of cytokines in pDCs was downregulated in response to stimulation with DNA and RNA viruses. Upon further investigation into the possible mechanism, we documented phosphorylation of STAT3 upon Ab-mediated engagement of TLR10. This leads to the induction of inhibitory molecule suppressor of cytokine signaling 3 (SOCS3) expression. We have also documented the inhibition of nuclear translocation of transcription factor IFN regulatory factor 7 (IRF7) in pDCs following TLR10 engagement. Our data provide the (to our knowledge) first evidence that TLR10 is constitutively expressed on the surface of human pDCs and works as a regulator of their innate response. Our findings indicate the potential of harnessing the function of pDCs by Ab-mediated targeting of TLR10 that may open a new therapeutic avenue for autoimmune disorders.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"577-587"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590461","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

Cutting Edge: Redundant Roles for MHC Class II-, CD1d-, and MR1-restricted T Cells in Clearing Bartonella Infection. 前沿：MHC II 类、CD1d 和 MR1 限制性 T 细胞在清除巴顿氏菌感染中的冗余作用。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2400045

Lena K Siewert, Katja Fromm, Christoph Dehio, Daniel D Pinschewer

{"title":"Cutting Edge: Redundant Roles for MHC Class II-, CD1d-, and MR1-restricted T Cells in Clearing Bartonella Infection.","authors":"Lena K Siewert, Katja Fromm, Christoph Dehio, Daniel D Pinschewer","doi":"10.4049/jimmunol.2400045","DOIUrl":"10.4049/jimmunol.2400045","url":null,"abstract":"The importance of unconventional T cells for mucosal immunity is firmly established but for systemic bacterial infection remains less well defined. In this study, we explored the role of various T cell subsets in murine Bartonella infection, which establishes persistent bacteremia unless controlled by antibacterial Abs. We found that αβ T cells are essential for Ab production against and clearance of B. taylorii, whereas MHC class I (MHC-I)- or MHC class II (MHC-II)-deficient mice eliminated B. taylorii infection with normal kinetics. Similarly, animals lacking either CD1d or MR1 suppressed bacteremia with normal kinetics. Interestingly, mice with a combined deficiency of either MHC-II and CD1d or MHC-II and MR1 failed to clear the infection, indicating that the combination of CD1d- and MR1-restricted T cells can compensate for the lack of MHC-II in this model. Our data document a previously underappreciated contribution of unconventional T cells to the control of systemic bacterial infection, supposedly as helper cells for antibacterial Ab production.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"553-558"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563510","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

Lung-resident CD3-NK1.1+CD69+CD103+ Cells Play an Important Role in Bacillus Calmette-Guérin Vaccine-Induced Protective Immunity against Mycobacterium tuberculosis Infection. 肺驻留 CD3-NK1.1+CD69+CD103+ 细胞在卡介苗诱导的结核分枝杆菌感染保护性免疫中发挥重要作用

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2200728

Olamipejo Durojaye, Abhinav Vankayalapati, Padmaja Paidipally, Tanmoy Mukherjee, Ramakrishna Vankayalapati, Rajesh Kumar Radhakrishnan

{"title":"Lung-resident CD3-NK1.1+CD69+CD103+ Cells Play an Important Role in Bacillus Calmette-Guérin Vaccine-Induced Protective Immunity against Mycobacterium tuberculosis Infection.","authors":"Olamipejo Durojaye, Abhinav Vankayalapati, Padmaja Paidipally, Tanmoy Mukherjee, Ramakrishna Vankayalapati, Rajesh Kumar Radhakrishnan","doi":"10.4049/jimmunol.2200728","DOIUrl":"10.4049/jimmunol.2200728","url":null,"abstract":"Tissue-resident immune cells play important roles in local tissue homeostasis and infection control. There is no information on the functional role of lung-resident CD3-NK1.1+CD69+CD103+ cells in intranasal Bacillus Calmette-Guérin (BCG)-vaccinated and/or Mycobacterium tuberculosis (Mtb)-infected mice. Therefore, we phenotypically and functionally characterized these cells in mice vaccinated intranasally with BCG. We found that intranasal BCG vaccination increased CD3-NK1.1+ cells with a tissue-resident phenotype (CD69+CD103+) in the lungs during the first 7 d after BCG vaccination. Three months post-BCG vaccination, Mtb infection induced the expansion of CD3-NK1.1+CD69+CD103+ (lung-resident) cells in the lung. Adoptive transfer of lung-resident CD3-NK1.1+CD69+CD103+ cells from the lungs of BCG-vaccinated mice to Mtb-infected naive mice resulted in a lower bacterial burden and reduced inflammation in the lungs. Our findings demonstrated that intranasal BCG vaccination induces the expansion of CD3-NK1.1+CD69+CD103+ (lung-resident) cells to provide protection against Mtb infection.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"669-677"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616661","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

ATM-dependent Phosphorylation of Nemo SQ Motifs Is Dispensable for Nemo-mediated Gene Expression Changes in Response to DNA Double-Strand Breaks. Nemo介导的基因表达变化对DNA双链断裂的响应离不开依赖ATM的Nemo SQ位点磷酸化。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2300139

Rebecca A Glynn, Katharina E Hayer, Craig H Bassing

{"title":"ATM-dependent Phosphorylation of Nemo SQ Motifs Is Dispensable for Nemo-mediated Gene Expression Changes in Response to DNA Double-Strand Breaks.","authors":"Rebecca A Glynn, Katharina E Hayer, Craig H Bassing","doi":"10.4049/jimmunol.2300139","DOIUrl":"10.4049/jimmunol.2300139","url":null,"abstract":"In response to DNA double-strand breaks (DSBs), the ATM kinase activates NF-κB factors to stimulate gene expression changes that promote survival and allow time for cells to repair damage. In cell lines, ATM can activate NF-κB transcription factors via two independent, convergent mechanisms. One is ATM-mediated phosphorylation of nuclear NF-κB essential modulator (Nemo) protein, which leads to monoubiquitylation and export of Nemo to the cytoplasm where it engages the IκB kinase (IKK) complex to activate NF-κB. Another is DSB-triggered migration of ATM into the cytoplasm, where it promotes monoubiquitylation of Nemo and the resulting IKK-mediated activation of NF-κB. ATM has many other functions in the DSB response beyond activation of NF-κB, and Nemo activates NF-κB downstream of diverse stimuli, including developmental or proinflammatory stimuli such as LPSs. To elucidate the in vivo role of DSB-induced, ATM-dependent changes in expression of NF-κB-responsive genes, we generated mice expressing phosphomutant Nemo protein lacking consensus SQ sites for phosphorylation by ATM or related kinases. We demonstrate that these mice are viable/healthy and fertile and exhibit overall normal B and T lymphocyte development. Moreover, treatment of their B lineage cells with LPS induces normal NF-κB-regulated gene expression changes. Furthermore, in marked contrast to results from a pre-B cell line, primary B lineage cells expressing phosphomutant Nemo treated with the genotoxic drug etoposide induce normal ATM- and Nemo-dependent changes in expression of NF-κB-regulated genes. Our data demonstrate that ATM-dependent phosphorylation of Nemo SQ motifs in vivo is dispensable for DSB-signaled changes in expression of NF-κB-regulated genes.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"628-640"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616659","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

CD39 Is Expressed on Functional Effector and Tissue-resident Memory CD8+ T Cells. CD39 在功能性效应细胞和组织驻留记忆 CD8+ T 细胞上表达。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2400151

Jordan F Isaacs, Hanna N Degefu, Tiffany Chen, Sierra A Kleist, Shawn C Musial, Myles A Ford, Tyler G Searles, Chun-Chieh Lin, Alexander G J Skorput, Keisuke Shirai, Mary Jo Turk, George J Zanazzi, Pamela C Rosato

{"title":"CD39 Is Expressed on Functional Effector and Tissue-resident Memory CD8+ T Cells.","authors":"Jordan F Isaacs, Hanna N Degefu, Tiffany Chen, Sierra A Kleist, Shawn C Musial, Myles A Ford, Tyler G Searles, Chun-Chieh Lin, Alexander G J Skorput, Keisuke Shirai, Mary Jo Turk, George J Zanazzi, Pamela C Rosato","doi":"10.4049/jimmunol.2400151","DOIUrl":"10.4049/jimmunol.2400151","url":null,"abstract":"The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on Ag-specific CD8+ short-lived effector cells, while it's co-ectoenzyme, CD73, is found on memory precursor effector cells (MPECs) in vivo. Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory T cell (TRM cell) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine TRM cells across several nonlymphoid tissues and melanoma, whereas CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ TRM cells are fully functional when stimulated ex vivo with cognate Ag, further expanding the identity of CD39 beyond a T cell exhaustion marker.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"588-599"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554963","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

Sepsis Impairs IFN-γ Production in CD8 T Cells through Changes in Local Chromatin Landscape. 败血症通过改变局部染色质景观影响 CD8 T 细胞产生 IFN-γ

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2300772

J Alejandro Cisneros-Segura, Noé Rodríguez-Rodríguez, Adrián Albarrán-Godínez, H Benjamín García-González, Carlos A Rodríguez-Osorio, Sergio Iván Valdés-Ferrer, Gustavo Tapia-Urzúa, Félix Recillas-Targa, Iris K Madera-Salcedo, Florencia Rosetti, José C Crispín

{"title":"Sepsis Impairs IFN-γ Production in CD8 T Cells through Changes in Local Chromatin Landscape.","authors":"J Alejandro Cisneros-Segura, Noé Rodríguez-Rodríguez, Adrián Albarrán-Godínez, H Benjamín García-González, Carlos A Rodríguez-Osorio, Sergio Iván Valdés-Ferrer, Gustavo Tapia-Urzúa, Félix Recillas-Targa, Iris K Madera-Salcedo, Florencia Rosetti, José C Crispín","doi":"10.4049/jimmunol.2300772","DOIUrl":"10.4049/jimmunol.2300772","url":null,"abstract":"Sepsis is a complex condition of inflammatory and immune dysregulation, triggered by severe infection. In survivors, chronic inflammation and immune dysregulation linger, facilitating the emergence of infections. CD8 dysfunction contributes to immunosuppression in sepsis survivors. We devised an animal model that enabled us to identify and analyze CD8-intrinsic defects induced by sepsis. We adoptively transferred CD45.1 CD8 OT-I T cells into CD45.2 congenic mice and subjected them to cecal ligature and puncture, to induce abdominal sepsis. One month later, we isolated the transferred CD8 cells. Surface marker expression confirmed they had not been activated through the TCR. CD8 OT-I T cells isolated from septic (or sham-operated) mice were transferred to second recipients, which were challenged with OVA-expressing Listeria monocytogenes. We compared effector capacities between OT-I cells exposed to sepsis and control cells. Naive mice that received OT-I cells exposed to sepsis had higher bacterial burden and a shorter survival when challenged with OVA-expressing L. monocytogenes. OT-I cells isolated from septic mice produced less IFN-γ but had conserved activation, expansion potential, and cytotoxic function. We observed lower transcript levels of IFN-γ and of the long noncoding RNA Ifng-as1, a local regulator of the epigenetic landscape, in cells exposed to sepsis. Accordingly, local abundance of a histone modification characteristic of active promoter regions was reduced in sepsis-exposed CD8 T cells. Our results identify a mechanism through which inflammation in the context of sepsis affects CD8 T cell function intrinsically.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"619-627"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734286","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

The Evolving Portrait of γδ TCR Recognition Determinants. γδTCR识别决定因素不断演变的形象。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2400114

Chhon Ling Sok, Jamie Rossjohn, Benjamin S Gully

引用次数: 0

Aryl Hydrocarbon Receptor Activation in Pulmonary Alveolar Epithelial Cells Limits Inflammation and Preserves Lung Epithelial Cell Integrity. 肺泡上皮细胞中芳基烃受体的激活可限制炎症并保护肺上皮细胞的完整性。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2300325

Elizabeth Zimmerman, Anne Sturrock, Christopher A Reilly, Katherine L Burrell-Gerbers, Kristi Warren, Mustafa Mir-Kasimov, Mingyang A Zhang, Megan S Pierce, My N Helms, Robert Paine

{"title":"Aryl Hydrocarbon Receptor Activation in Pulmonary Alveolar Epithelial Cells Limits Inflammation and Preserves Lung Epithelial Cell Integrity.","authors":"Elizabeth Zimmerman, Anne Sturrock, Christopher A Reilly, Katherine L Burrell-Gerbers, Kristi Warren, Mustafa Mir-Kasimov, Mingyang A Zhang, Megan S Pierce, My N Helms, Robert Paine","doi":"10.4049/jimmunol.2300325","DOIUrl":"10.4049/jimmunol.2300325","url":null,"abstract":"The aryl hydrocarbon receptor (AHR) is a receptor/transcription factor widely expressed in the lung. The physiological roles of AHR expressed in the alveolar epithelium remain unclear. In this study, we tested the hypothesis that alveolar epithelial AHR activity plays an important role in modulating inflammatory responses and maintaining alveolar integrity during lung injury and repair. AHR is expressed in alveolar epithelial cells (AECs) and is active. AHR activation with the endogenous AHR ligand, FICZ (5,11-dihydroindolo[3,2-b] carbazole-6-carboxaldehyde), significantly suppressed inflammatory cytokine expression in response to inflammatory stimuli in primary murine AECs and in the MLE-15 epithelial cell line. In an LPS model of acute lung injury in mice, coadministration of FICZ with LPS suppressed protein leak, reduced neutrophil accumulation in BAL fluid, and suppressed inflammatory cytokine expression in lung tissue and BAL fluid. Relevant to healing following inflammatory injury, AHR activation suppressed TGF-β-induced expression of genes associated with epithelial-mesenchymal transition. Knockdown of AHR in primary AECs with shRNA or in CRISPR-Cas-9-induced MLE-15 cells resulted in upregulation of α-smooth muscle actin (αSma), Col1a1, and Fn1 and reduced expression of epithelial genes Col4a1 and Sdc1. MLE-15 clones lacking AHR demonstrated accelerated wound closure in a scratch model. AHR activation with FICZ enhanced barrier function (transepithelial electrical resistance) in primary murine AECs and limited decline of transepithelial electrical resistance following inflammatory injury. AHR activation in AECs preserves alveolar integrity by modulating inflammatory cytokine expression while enhancing barrier function and limiting stress-induced expression of mesenchymal genes.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"600-611"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734285","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