ImmunoHorizons最新文献

筛选
英文 中文
Embigin Is Highly Expressed on CD4+ and CD8+ T Cells but Is Dispensable for Several T Cell Effector Responses. Embigin在CD4+和CD8+T细胞上高表达,但在几种T细胞效应反应中是不可或缺的。
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300083
Haoran Yang, Naoki Iwanaga, Alexis R Katz, Andy R Ridley, Haiyan D Miller, Michaela J Allen, Dereck Pociask, Jay K Kolls
{"title":"Embigin Is Highly Expressed on CD4+ and CD8+ T Cells but Is Dispensable for Several T Cell Effector Responses.","authors":"Haoran Yang, Naoki Iwanaga, Alexis R Katz, Andy R Ridley, Haiyan D Miller, Michaela J Allen, Dereck Pociask, Jay K Kolls","doi":"10.4049/immunohorizons.2300083","DOIUrl":"10.4049/immunohorizons.2300083","url":null,"abstract":"<p><p>T cell immunity, including CD4+ and CD8+ T cell immunity, is critical to host immune responses to infection. Transcriptomic analyses of both CD4+ and CD8+ T cells of C57BL/6 mice show high expression the gene encoding embigin, Emb, which encodes a transmembrane glycoprotein. Moreover, we found that lung CD4+ Th17 tissue-resident memory T cells of C57BL/6 mice also express high levels of Emb. However, deletion of Emb in αβ T cells of C57BL/6 mice revealed that Emb is dispensable for thymic T cell development, generation of lung Th17 tissue-resident memory T cells, tissue-resident memory T cell homing to the lung, experimental autoimmune encephalitis, as well as clearance of pulmonary viral or fungal infection. Thus, based on this study, embigin appears to play a minor role if any in αβ T cell development or αβ T cell effector functions in C57BL/6 mice.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041201","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}
引用次数: 0
Fatty Acids Play a Critical Role in Mitochondrial Oxidative Phosphorylation in Effector T Cells in Graft-versus-Host Disease. 脂肪酸在移植物抗宿主疾病效应 T 细胞线粒体氧化磷酸化过程中发挥关键作用
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300115
Hirofumi Nakano, Kazuya Sato, Junko Izawa, Norihito Takayama, Hiroko Hayakawa, Takashi Ikeda, Shin-Ichiro Kawaguchi, Kiyomi Mashima, Kento Umino, Kaoru Morita, Ryoji Ito, Nobuhiko Ohno, Kaoru Tominaga, Hitoshi Endo, Yoshinobu Kanda
{"title":"Fatty Acids Play a Critical Role in Mitochondrial Oxidative Phosphorylation in Effector T Cells in Graft-versus-Host Disease.","authors":"Hirofumi Nakano, Kazuya Sato, Junko Izawa, Norihito Takayama, Hiroko Hayakawa, Takashi Ikeda, Shin-Ichiro Kawaguchi, Kiyomi Mashima, Kento Umino, Kaoru Morita, Ryoji Ito, Nobuhiko Ohno, Kaoru Tominaga, Hitoshi Endo, Yoshinobu Kanda","doi":"10.4049/immunohorizons.2300115","DOIUrl":"10.4049/immunohorizons.2300115","url":null,"abstract":"<p><p>Although the role of aerobic glycolysis in activated T cells has been well characterized, whether and how fatty acids (FAs) contribute to donor T cell function in allogeneic hematopoietic stem cell transplantation is unclear. Using xenogeneic graft-versus-host disease (GVHD) models, this study demonstrated that exogenous FAs serve as a crucial source of mitochondrial respiration in donor T cells in humans. By comparing human T cells isolated from wild-type NOD/Shi-scid-IL2rγnull (NOG) mice with those from MHC class I/II-deficient NOG mice, we found that donor T cells increased extracellular FA uptake, the extent of which correlates with their proliferation, and continued to increase FA uptake during effector differentiation. Gene expression analysis showed the upregulation of a wide range of lipid metabolism-related genes, including lipid hydrolysis, mitochondrial FA transport, and FA oxidation. Extracellular flux analysis demonstrated that mitochondrial FA transport was required to fully achieve the mitochondrial maximal respiration rate and spare respiratory capacity, whereas the substantial disruption of glucose supply by either glucose deprivation or mitochondrial pyruvate transport blockade did not impair oxidative phosphorylation. Taken together, FA-driven mitochondrial respiration is a hallmark that differentiates TCR-dependent T cell activation from TCR-independent immune response after hematopoietic stem cell transplant.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029851","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}
引用次数: 0
Peptidoglycan from Bacillus anthracis Inhibits Human Macrophage Efferocytosis in Part by Reducing Cell Surface Expression of MERTK and TIM-3. 炭疽杆菌的肽聚糖部分通过降低细胞表面 MERTK 和 TIM-3 的表达抑制人类巨噬细胞的吞噬作用
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300109
Joshua S Mytych, Zijian Pan, Charmaine Lopez-Davis, Nancy Redinger, Christina Lawrence, Jadith Ziegler, Narcis I Popescu, Judith A James, A Darise Farris
{"title":"Peptidoglycan from Bacillus anthracis Inhibits Human Macrophage Efferocytosis in Part by Reducing Cell Surface Expression of MERTK and TIM-3.","authors":"Joshua S Mytych, Zijian Pan, Charmaine Lopez-Davis, Nancy Redinger, Christina Lawrence, Jadith Ziegler, Narcis I Popescu, Judith A James, A Darise Farris","doi":"10.4049/immunohorizons.2300109","DOIUrl":"10.4049/immunohorizons.2300109","url":null,"abstract":"<p><p>Bacillus anthracis peptidoglycan (PGN) is a major component of the bacterial cell wall and a key pathogen-associated molecular pattern contributing to anthrax pathology, including organ dysfunction and coagulopathy. Increases in apoptotic leukocytes are a late-stage feature of anthrax and sepsis, suggesting there is a defect in apoptotic clearance. In this study, we tested the hypothesis that B. anthracis PGN inhibits the capacity of human monocyte-derived macrophages (MΦ) to efferocytose apoptotic cells. Exposure of CD163+CD206+ MΦ to PGN for 24 h impaired efferocytosis in a manner dependent on human serum opsonins but independent of complement component C3. PGN treatment reduced cell surface expression of the proefferocytic signaling receptors MERTK, TYRO3, AXL, integrin αVβ5, CD36, and TIM-3, whereas TIM-1, αVβ3, CD300b, CD300f, STABILIN-1, and STABILIN-2 were unaffected. ADAM17 is a major membrane-bound protease implicated in mediating efferocytotic receptor cleavage. We found multiple ADAM17-mediated substrates increased in PGN-treated supernatant, suggesting involvement of membrane-bound proteases. ADAM17 inhibitors TAPI-0 and Marimastat prevented TNF release, indicating effective protease inhibition, and modestly increased cell-surface levels of MerTK and TIM-3 but only partially restored efferocytic capacity by PGN-treated MΦ. We conclude that human serum factors are required for optimal recognition of PGN by human MΦ and that B. anthracis PGN inhibits efferocytosis in part by reducing cell surface expression of MERTK and TIM-3.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186745","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}
引用次数: 0
Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development. SARS-CoV-2 Spike 蛋白的免疫表位和通用疫苗开发的考虑因素。
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2400003
Nicholas Magazine, Tianyi Zhang, Anang D Bungwon, Michael C McGee, Yingying Wu, Gianluca Veggiani, Weishan Huang
{"title":"Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development.","authors":"Nicholas Magazine, Tianyi Zhang, Anang D Bungwon, Michael C McGee, Yingying Wu, Gianluca Veggiani, Weishan Huang","doi":"10.4049/immunohorizons.2400003","DOIUrl":"10.4049/immunohorizons.2400003","url":null,"abstract":"<p><p>Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable of evading prior immunity. The mutation and evolution of SARS-CoV-2 have created a demand for persistent efforts in vaccine development. SARS-CoV-2 Spike protein has been the primary target for COVID-19 vaccine development, but it is also the hotspot of mutations directly involved in host susceptibility and virus immune evasion. Our ability to predict emerging mutants and select conserved epitopes is critical for the development of a broadly neutralizing therapy or a universal vaccine. In this article, we review the general paradigm of immune responses to COVID-19 vaccines, highlighting the immunological epitopes of Spike protein that are likely associated with eliciting protective immunity resulting from vaccination in humans. Specifically, we analyze the structural and evolutionary characteristics of the SARS-CoV-2 Spike protein related to immune activation and function via the TLRs, B cells, and T cells. We aim to provide a comprehensive analysis of immune epitopes of Spike protein, thereby contributing to the development of new strategies for broad neutralization or universal vaccination.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998713","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}
引用次数: 0
SARS-CoV-2 Vaccine-Elicited Immunity after B Cell Depletion in Multiple Sclerosis. 多发性硬化症 B 细胞耗竭后 SARS-CoV-2 疫苗激发的免疫力
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300108
Ryan M Baxter, Berenice Cabrera-Martinez, Tusharkanti Ghosh, Cody Rester, Miguel Guerrero Moreno, Tyler L Borko, Sean Selva, Chelsie L Fleischer, Nicola Haakonsen, Ariana Mayher, Emily Bowhay, Courtney Evans, Todd M Miller, Leah Huey, Jennifer McWilliams, Adrie van Bokhoven, Kevin D Deane, Vijaya Knight, Kimberly R Jordan, Debashis Ghosh, Jared Klarquist, Ross M Kedl, Amanda L Piquet, Elena W Y Hsieh
{"title":"SARS-CoV-2 Vaccine-Elicited Immunity after B Cell Depletion in Multiple Sclerosis.","authors":"Ryan M Baxter, Berenice Cabrera-Martinez, Tusharkanti Ghosh, Cody Rester, Miguel Guerrero Moreno, Tyler L Borko, Sean Selva, Chelsie L Fleischer, Nicola Haakonsen, Ariana Mayher, Emily Bowhay, Courtney Evans, Todd M Miller, Leah Huey, Jennifer McWilliams, Adrie van Bokhoven, Kevin D Deane, Vijaya Knight, Kimberly R Jordan, Debashis Ghosh, Jared Klarquist, Ross M Kedl, Amanda L Piquet, Elena W Y Hsieh","doi":"10.4049/immunohorizons.2300108","DOIUrl":"10.4049/immunohorizons.2300108","url":null,"abstract":"<p><p>The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121681","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}
引用次数: 0
PD-1 Limits IL-2 Production and Thymic Regulatory T Cell Development. PD-1 限制 IL-2 的产生和胸腺调节性 T 细胞的发育
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300079
Breanna Caruso, Benjamin R Weeder, Reid F Thompson, Amy E Moran
{"title":"PD-1 Limits IL-2 Production and Thymic Regulatory T Cell Development.","authors":"Breanna Caruso, Benjamin R Weeder, Reid F Thompson, Amy E Moran","doi":"10.4049/immunohorizons.2300079","DOIUrl":"10.4049/immunohorizons.2300079","url":null,"abstract":"<p><p>Inhibitory proteins, such as programmed cell death protein 1 (PD-1), have been studied extensively in peripheral T cell responses to foreign Ags, self-Ags, and neoantigens. Notably, these proteins are first expressed during T cell development in the thymus. Reports suggest that PD-1 limits regulatory T cell (Treg) development, but the mechanism by which PD-1 exerts this function remains unknown. The present study expands the evaluation of murine PD-1 and its ligands in the thymus, demonstrating that some of the highest expressers of PD-1 and programmed death-ligand 1 are agonist selected cells. Surprisingly, we reveal a selective role for PD-1 in regulating the developmental niche only for Tregs because other agonist selected cell populations, such as NK T cells, remain unchanged. We also ruled out PD-1 as a regulator of proliferation or cell death of agonist selected Tregs and further demonstrated that PD-1-deficient Tregs have reduced TCR signaling. Unexpectedly, the data suggest that PD-1-deficient thymocytes produce elevated levels of IL-2, a Treg niche-limiting cytokine. Collectively, these data suggest a novel role for PD-1 in regulating IL-2 production and the concurrent agonist selection of murine thymic Tregs. This observation has implications for the use of checkpoint blockade in the context of cancer and infection.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320247","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}
引用次数: 0
Erdr1 Drives Macrophage Programming via Dynamic Interplay with YAP1 and Mid1. Erdr1通过与YAP1和Mid1的动态相互作用驱动巨噬细胞编程
ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2400004
Yuhang Wang
{"title":"Erdr1 Drives Macrophage Programming via Dynamic Interplay with YAP1 and Mid1.","authors":"Yuhang Wang","doi":"10.4049/immunohorizons.2400004","DOIUrl":"10.4049/immunohorizons.2400004","url":null,"abstract":"<p><p>Erythroid differentiation regulator 1 (Erdr1) is a stress-induced, widely expressed, highly conserved secreted factor found in both humans and mice. Erdr1 is linked with the Hippo-YAP1 signaling. Initially identified as an inducer of hemoglobin synthesis, Erdr1 emerged as a multifunctional protein, especially in immune cells. Although Erdr1 has been implicated in regulating T cells and NK cell function, its role in macrophage remains unclear. This study explored the function and mechanism of Erdr1 in macrophage inflammatory response. The data demonstrated that Erdr1 could promote anti-inflammatory cytokine production, a function that also has been reported by previous research. However, I found Erdr1 also could play a proinflammatory role. The function of Erdr1 in macrophages depends on its dose and cell density. I observed that Erdr1 expression was inhibited in M1 macrophages but was upregulated in M2 macrophages compared with unpolarized macrophages. I hypothesized that Erdr1 balances the inflammatory response by binding with distinct adaptors dependent on varying concentrations. Mechanistically, I demonstrated YAP1 and Mid1 as the two adaptor proteins of Erdr1. The Erdr1-YAP1 interaction promotes anti-inflammatory cytokine production when Erdr1 levels are elevated, whereas the Erdr1-Mid1 interaction induces proinflammatory cytokine production when Erdr1 levels are decreased. This study highlights the effects of Erdr1 on regulating cytokine production from polarized macrophages potentially by regulating YAP1 in the nonclassical Hippo pathway.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934694","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}
引用次数: 0
Persistent B Cell-Derived MHC Class II Signaling Is Required for the Optimal Maintenance of Tissue-Resident Helper T Cells. 组织驻留辅助性 T 细胞的最佳维持需要持续的 B 细胞衍生 MHC II 类信号。
ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2300093
Young Min Son, In Su Cheon, Chaofan Li, Jie Sun
{"title":"Persistent B Cell-Derived MHC Class II Signaling Is Required for the Optimal Maintenance of Tissue-Resident Helper T Cells.","authors":"Young Min Son, In Su Cheon, Chaofan Li, Jie Sun","doi":"10.4049/immunohorizons.2300093","DOIUrl":"10.4049/immunohorizons.2300093","url":null,"abstract":"<p><p>Emerging studies have identified the critical roles of tissue-resident memory CD8+ T (TRM) and B (BRM) cells in the protection against mucosal viral infections, but the underlying mechanisms regulating robust development of TRM and BRM cells remain incompletely understood. We have recently shown that tissue-resident helper CD4+ T (TRH) cells, developed following influenza virus infection, function to sustain the optimal maintenance of TRM and BRM cells at the mucosal surface. In this study, we have explored the cellular and molecular cues modulating lung TRH persistence after influenza infection in C57BL/6 mice. We found that TRH cells were colocalized in tertiary lymphoid structures (TLSs) with local B cells. Abolishing TLSs or the depletion of B cells impaired lung TRH cell numbers. Of note, we found that persistent TCR signaling is needed for the maintenance of TRH cells after the clearance of infectious influenza virus. Furthermore, selective ablation of B cell-derived MHC class II resulted in partial reduction of lung TRH cell number after influenza infection. Our findings suggest that the interaction between lung-resident TRH cells and B cells, along with persistent Ag stimulation, is required to maintain TRH cells after respiratory viral infection.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725450","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}
引用次数: 0
GSK3α/β Restrain IFN-γ-Inducible Costimulatory Molecule Expression in Alveolar Macrophages, Limiting CD4+ T Cell Activation. GSK3α/β 可抑制肺泡巨噬细胞中 IFN-γ 诱导性成本调控分子的表达,从而限制 CD4+ T 细胞的活化。
ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2300107
Laurisa M Ankley, Kayla N Conner, Taryn E Vielma, Jared J Godfrey, Mahima Thapa, Andrew J Olive
{"title":"GSK3α/β Restrain IFN-γ-Inducible Costimulatory Molecule Expression in Alveolar Macrophages, Limiting CD4+ T Cell Activation.","authors":"Laurisa M Ankley, Kayla N Conner, Taryn E Vielma, Jared J Godfrey, Mahima Thapa, Andrew J Olive","doi":"10.4049/immunohorizons.2300107","DOIUrl":"10.4049/immunohorizons.2300107","url":null,"abstract":"<p><p>Macrophages play a crucial role in eliminating respiratory pathogens. Both pulmonary resident alveolar macrophages (AMs) and recruited macrophages contribute to detecting, responding to, and resolving infections in the lungs. Despite their distinct functions, it remains unclear how these macrophage subsets regulate their responses to infection, including how activation by the cytokine IFN-γ is regulated. This shortcoming prevents the development of therapeutics that effectively target distinct lung macrophage populations without exacerbating inflammation. We aimed to better understand the transcriptional regulation of resting and IFN-γ-activated cells using a new ex vivo model of AMs from mice, fetal liver-derived alveolar-like macrophages (FLAMs), and immortalized bone marrow-derived macrophages. Our findings reveal that IFN-γ robustly activates both macrophage types; however, the profile of activated IFN-γ-stimulated genes varies greatly between these cell types. Notably, FLAMs show limited expression of costimulatory markers essential for T cell activation upon stimulation with only IFN-γ. To understand cell type-specific differences, we examined how the inhibition of the regulatory kinases GSK3α/β alters the IFN-γ response. GSK3α/β controlled distinct IFN-γ responses, and in AM-like cells, we found that GSK3α/β restrained the induction of type I IFN and TNF, thus preventing the robust expression of costimulatory molecules and limiting CD4+ T cell activation. Together, these data suggest that the capacity of AMs to respond to IFN-γ is restricted in a GSK3α/β-dependent manner and that IFN-γ responses differ across distinct macrophage populations. These findings lay the groundwork to identify new therapeutic targets that activate protective pulmonary responses without driving deleterious inflammation.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725449","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}
引用次数: 0
A Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs. 利用月经盘对女性下生殖道免疫细胞进行采样的无创方法
ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2300105
M Quinn Peters, Eva Domenjo-Vila, Marc Carlson, Blair Armistead, Paul T Edlefsen, Melanie Gasper, Smritee Dabee, Christopher Whidbey, Heather B Jaspan, Martin Prlic, Whitney E Harrington
{"title":"A Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs.","authors":"M Quinn Peters, Eva Domenjo-Vila, Marc Carlson, Blair Armistead, Paul T Edlefsen, Melanie Gasper, Smritee Dabee, Christopher Whidbey, Heather B Jaspan, Martin Prlic, Whitney E Harrington","doi":"10.4049/immunohorizons.2300105","DOIUrl":"10.4049/immunohorizons.2300105","url":null,"abstract":"<p><p>T cells in the human female genital tract (FGT) are key mediators of susceptibility to and protection from infection, including HIV and other sexually transmitted infections. There is a critical need for increased understanding of the distribution and activation of T cell populations in the FGT, but current sampling methods require a healthcare provider and are expensive, limiting the ability to study these populations longitudinally. To address these challenges, we have developed a method to sample immune cells from the FGT utilizing disposable menstrual discs which are noninvasive, self-applied, and low in cost. To demonstrate reproducibility, we sampled the cervicovaginal fluid of healthy, reproductive-aged individuals using menstrual discs across 3 sequential days. Cervicovaginal fluid was processed for cervicovaginal cells, and high-parameter flow cytometry was used to characterize immune populations. We identified large numbers of live, CD45+ leukocytes, as well as distinct populations of T cells and B cells. Within the T cell compartment, activation and suppression status of T cell subsets were consistent with previous studies of the FGT utilizing current approaches, including identification of both tissue-resident and migratory populations. In addition, the T cell population structure was highly conserved across days within individuals but divergent across individuals. Our approach to sample immune cells in the FGT with menstrual discs will decrease barriers to participation and empower longitudinal sampling in future research studies.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934693","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信