Journal of immunology最新文献_第4页

Mitochondrial DNA Programs Lactylation of cGAS to Induce IFN Responses in Patients with Systemic Lupus Erythematosus. 线粒体 DNA 对 cGAS 进行乳化编程，诱导系统性红斑狼疮患者产生 IFN 反应。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-15 DOI: 10.4049/jimmunol.2300758

Juan Zhang, Huiyan Ji, Mengdi Liu, Ming Zheng, Zhenke Wen, Haili Shen

{"title":"Mitochondrial DNA Programs Lactylation of cGAS to Induce IFN Responses in Patients with Systemic Lupus Erythematosus.","authors":"Juan Zhang, Huiyan Ji, Mengdi Liu, Ming Zheng, Zhenke Wen, Haili Shen","doi":"10.4049/jimmunol.2300758","DOIUrl":"10.4049/jimmunol.2300758","url":null,"abstract":"Mitochondrial DNA (mtDNA) is frequently released from mitochondria, activating cGAS-STING signaling and inducing type I IFNs (IFN-Is) in systemic lupus erythematosus (SLE). Meanwhile, whether and how the glycolytic pathway was involved in such IFN-I responses in human SLE remain unclear. In this study, we found that monocytes from SLE patients exerted robust IFN-I generation and elevated level of cytosolic mtDNA. Transfection of mtDNA into THP-1 macrophages was efficient in inducing IFN-I responses, together with the strong glycolytic pathway that promoted lactate production, mimicking the SLE phenotype. Blockade of lactate generation abrogated such IFN-I responses and, vice versa, exogenous lactate enhanced the IFN-I generation. Mechanistically, lactate promoted the lactylation of cGAS, which inhibited its binding to E3 ubiquitination ligase MARCHF5, blocking cGAS degradation and leading to strong IFN-I responses. In accordance, targeting lactate generation alleviated disease development in humanized SLE chimeras. Collectively, cytosolic mtDNA drives metabolic adaption toward the glycolytic pathway, promoting lactylation of cGAS for licensing IFN-I responses in human SLE and thereby assigning the glycolytic pathway as a promising therapeutic target for SLE.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"795-807"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875011","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

Vaccination with O-linked Mannans Protects against Systemic Candidiasis through Innate Lymphocyte Populations. 接种 O 链甘露聚糖疫苗可通过先天性淋巴细胞群预防全身性念珠菌病

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-15 DOI: 10.4049/jimmunol.2400065

Cleison Ledesma Taira, Lucas Dos Santos Dias, Sarah Lichtenberger, Alexander J Whitehead, Brenda Kischkel, Mihai G Netea, Bruce S Klein, Marcel Wüthrich

{"title":"Vaccination with O-linked Mannans Protects against Systemic Candidiasis through Innate Lymphocyte Populations.","authors":"Cleison Ledesma Taira, Lucas Dos Santos Dias, Sarah Lichtenberger, Alexander J Whitehead, Brenda Kischkel, Mihai G Netea, Bruce S Klein, Marcel Wüthrich","doi":"10.4049/jimmunol.2400065","DOIUrl":"10.4049/jimmunol.2400065","url":null,"abstract":"Candida spp. are the fourth leading cause of bloodstream infections in hospitalized patients and the most common cause of invasive fungal infection. No vaccine against Candida spp. or other fungal pathogens of humans is available. We recently discovered the Blastomyces Dectin-2 ligand endoglucanase 2 that harbors antigenic and adjuvant functions and can function as a protective vaccine against that fungus. We also reported that the adjuvant activity, which is mediated by O-mannans decorating the C terminus of Blastomyces Dectin-2 ligand endoglucanase 2, can augment peptide Ag-induced vaccine immunity against heterologous agents, including Cryptococcus, Candida, and influenza. In this article, we report that the O-linked mannans alone, in the absence of any antigenic peptide, can also protect against systemic candidiasis, reducing kidney fungal load and increasing survival in a Dectin-2-dependent manner. We found that this long-term glycan-induced protection is mediated by innate lymphocyte populations including TCR-γδ+ T cells, innate lymphoid cells, and NK cells that subsequently activate and release reactive oxygen species from neutrophils and monocytes. Our findings suggest that Blastomyces O-mannan displayed by Eng2 induces a form of protective trained immunity mediated by innate lymphocyte populations.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"843-852"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897621","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

Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-β Antibodies. 新型人中和性抗 IFN-α 和抗 IFN-β 抗体的克隆与功能特征。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-15 DOI: 10.4049/jimmunol.2400265

Emmanouil Papasavvas, Lily Lu, Matthew Fair, Isabela Oliva, Joel Cassel, Sonali Majumdar, Karam Mounzer, Jay R Kostman, Pablo Tebas, Amit Bar-Or, Kar Muthumani, Luis J Montaner

{"title":"Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-β Antibodies.","authors":"Emmanouil Papasavvas, Lily Lu, Matthew Fair, Isabela Oliva, Joel Cassel, Sonali Majumdar, Karam Mounzer, Jay R Kostman, Pablo Tebas, Amit Bar-Or, Kar Muthumani, Luis J Montaner","doi":"10.4049/jimmunol.2400265","DOIUrl":"10.4049/jimmunol.2400265","url":null,"abstract":"Type I IFNs play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-β Abs from PBMCs of individuals treated with IFN-α or IFN-β, harboring confirmed neutralizing Abs. Clones AH07856 and AH07857 were identified as neutralizing anti-IFN-α-specific with inhibition against IFN-α2a, -α2b, and -αK subtypes. Clones AH07859 and AH07866 were identified as neutralizing anti-IFN-β1a-specific signaling and able to block lipopolysaccharide or S100 calcium-binding protein A14-induced IFN-β signaling effects. Cloned Abs bind rhesus but not murine IFNs. The specificity of inhibition between IFN-α and IFN-β suggests potential for diverse research and clinical applications.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"808-822"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897619","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

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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Crystal Structure of the Michaelis-Menten Complex of C1 Esterase Inhibitor and C1s Reveals Novel Insights into Complement Regulation. C1 酯酶抑制剂和 C1s 的 Michaelis-Menten 复合物晶体结构揭示了补体调节的新观点。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-01 DOI: 10.4049/jimmunol.2400194

Ryan J Garrigues, Matthew P Garrison, Brandon L Garcia

{"title":"The Crystal Structure of the Michaelis-Menten Complex of C1 Esterase Inhibitor and C1s Reveals Novel Insights into Complement Regulation.","authors":"Ryan J Garrigues, Matthew P Garrison, Brandon L Garcia","doi":"10.4049/jimmunol.2400194","DOIUrl":"10.4049/jimmunol.2400194","url":null,"abstract":"The ancient arm of innate immunity known as the complement system is a blood proteolytic cascade involving dozens of membrane-bound and solution-phase components. Although many of these components serve as regulatory molecules to facilitate controlled activation of the cascade, C1 esterase inhibitor (C1-INH) is the sole canonical complement regulator belonging to a superfamily of covalent inhibitors known as serine protease inhibitors (SERPINs). In addition to its namesake role in complement regulation, C1-INH also regulates proteases of the coagulation, fibrinolysis, and contact pathways. Despite this, the structural basis for C1-INH recognition of its target proteases has remained elusive. In this study, we present the crystal structure of the Michaelis-Menten (M-M) complex of the catalytic domain of complement component C1s and the SERPIN domain of C1-INH at a limiting resolution of 3.94 Å. Analysis of the structure revealed that nearly half of the protein/protein interface is formed by residues outside of the C1-INH reactive center loop. The contribution of these residues to the affinity of the M-M complex was validated by site-directed mutagenesis using surface plasmon resonance. Parallel analysis confirmed that C1-INH-interfacing residues on C1s surface loops distal from the active site also drive affinity of the M-M complex. Detailed structural comparisons revealed differences in substrate recognition by C1s compared with C1-INH recognition and highlight the importance of exosite interactions across broader SERPIN/protease systems. Collectively, this study improves our understanding of how C1-INH regulates the classical pathway of complement, and it sheds new light on how SERPINs recognize their cognate protease targets.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"718-729"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590460","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

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