ImmunoHorizons最新文献_第8页

Sodium-Glucose Cotransporter-2 Inhibitor, Empagliflozin, Suppresses the Inflammatory Immune Response to Influenza Infection. 葡萄糖钠转运体 2 抑制剂 Empagliflozin 可抑制流感感染的炎症免疫反应

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300077

Nicholas J Constantinesco, Baskaran Chinnappan, Louis J DeVito, Crystal Moras, Sashwath Srikanth, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Radha Gopal

{"title":"Sodium-Glucose Cotransporter-2 Inhibitor, Empagliflozin, Suppresses the Inflammatory Immune Response to Influenza Infection.","authors":"Nicholas J Constantinesco, Baskaran Chinnappan, Louis J DeVito, Crystal Moras, Sashwath Srikanth, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Radha Gopal","doi":"10.4049/immunohorizons.2300077","DOIUrl":"10.4049/immunohorizons.2300077","url":null,"abstract":"Influenza is a highly contagious, acute respiratory disease that causes significant public health and economic threats. Influenza infection induces various inflammatory mediators, IFNs, and recruitment of inflammatory cells in the host. This inflammatory \"cytokine storm\" is thought to play a role in influenza-induced lung pathogenesis. Empagliflozin is a drug primarily used to lower blood glucose in type II diabetes patients by inhibiting the sodium-glucose cotransporter-2 (SGLT-2) found in the proximal tubules in the kidneys. In this study, we have investigated the effects of empagliflozin on the pulmonary immune response to influenza infection. C57BL/6 mice (wild type) were infected with influenza A/PR/8/34 and treated with empagliflozin, and the disease outcomes were analyzed. Empagliflozin treatment decreased the expression of the inflammatory cytokines IL-1β, IL-6, and CCL2; the percentage of inflammatory monocytes and inducible NO synthase-positive macrophages; and IFN response genes Stat1 and CXCL9 during influenza infection. Further, empagliflozin treatment decreases the expression of IL-6, CCL2, and CCL5 in RAW264.7 macrophages and bone marrow-derived macrophages. However, empagliflozin treatment increased influenza viral titer during infection. Despite fostering an increased viral burden, treatment with empagliflozin decreases the mortality in wild type and high fat diet-induced atherosclerotic LDLR-/- mice. Based on our findings, empagliflozin may have therapeutic implications for use in patients to prevent lung damage and acute respiratory illness.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815121","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

Egr2 Deletion in Autoimmune-Prone C57BL6/lpr Mice Suppresses the Expression of Methylation-Sensitive Dlk1-Dio3 Cluster MicroRNAs. 自身免疫易感性 C57BL6/lpr 小鼠的 Egr2 基因缺失抑制甲基化敏感的 Dlk1-Dio3 簇 MicroRNAs 的表达

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300111

Zhuang Wang, Bettina Heid, Jianlin He, Hehuang Xie, Christopher M Reilly, Rujuan Dai, S Ansar Ahmed

{"title":"Egr2 Deletion in Autoimmune-Prone C57BL6/lpr Mice Suppresses the Expression of Methylation-Sensitive Dlk1-Dio3 Cluster MicroRNAs.","authors":"Zhuang Wang, Bettina Heid, Jianlin He, Hehuang Xie, Christopher M Reilly, Rujuan Dai, S Ansar Ahmed","doi":"10.4049/immunohorizons.2300111","DOIUrl":"10.4049/immunohorizons.2300111","url":null,"abstract":"We previously demonstrated that the upregulation of microRNAs (miRNAs) at the genomic imprinted Dlk1-Dio3 locus in murine lupus is correlated with global DNA hypomethylation. We now report that the Dlk1-Dio3 genomic region in CD4+ T cells of MRL/lpr mice is hypomethylated, linking it to increased Dlk1-Dio3 miRNA expression. We evaluated the gene expression of methylating enzymes, DNA methyltransferases (DNMTs), and demethylating ten-eleven translocation proteins (TETs) to elucidate the molecular basis of DNA hypomethylation in lupus CD4+ T cells. There was a significantly elevated expression of Dnmt1 and Dnmt3b, as well as Tet1 and Tet2, in CD4+ T cells of three different lupus-prone mouse strains compared to controls. These findings suggest that the hypomethylation of murine lupus CD4+ T cells is likely attributed to a TET-mediated active demethylation pathway. Moreover, we found that deletion of early growth response 2 (Egr2), a transcription factor gene in B6/lpr mice markedly reduced maternally expressed miRNA genes but not paternally expressed protein-coding genes at the Dlk1-Dio3 locus in CD4+ T cells. EGR2 has been shown to induce DNA demethylation by recruiting TETs. Surprisingly, we found that deleting Egr2 in B6/lpr mice induced more hypomethylated differentially methylated regions at either the whole-genome level or the Dlk1-Dio3 locus in CD4+ T cells. Although the role of methylation in EGR2-mediated regulation of Dlk1-Dio3 miRNAs is not readily apparent, these are the first data to show that in lupus, Egr2 regulates Dlk1-Dio3 miRNAs, which target major signaling pathways in autoimmunity. These data provide a new perspective on the role of upregulated EGR2 in lupus pathogenesis.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139050008","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

Intravascular Leukocyte Labeling Refines the Distribution of Myeloid Cells in the Lung in Models of Allergen-induced Airway Inflammation. 血管内白细胞标记细化了过敏原诱发气道炎症模型中肺部髓系细胞的分布。

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300059

Yu-Hua Chow, Ryan C Murphy, Dowon An, Ying Lai, William A Altemeier, Anne M Manicone, Teal S Hallstrand

{"title":"Intravascular Leukocyte Labeling Refines the Distribution of Myeloid Cells in the Lung in Models of Allergen-induced Airway Inflammation.","authors":"Yu-Hua Chow, Ryan C Murphy, Dowon An, Ying Lai, William A Altemeier, Anne M Manicone, Teal S Hallstrand","doi":"10.4049/immunohorizons.2300059","DOIUrl":"10.4049/immunohorizons.2300059","url":null,"abstract":"Innate immune cell populations are critical in asthma with different functional characteristics based on tissue location, which has amplified the importance of characterizing the precise number and location of innate immune populations in murine models of asthma. In this study, we performed premortem intravascular (IV) labeling of leukocytes in mice in two models of asthma to differentiate innate immune cell populations within the IV compartment versus those residing in the lung tissue or airway lumen. We performed spectral flow cytometry analysis of the blood, suspensions of digested lung tissue, and bronchoalveolar lavage fluid. We discovered that IV labeled leukocytes do not contaminate analysis of bronchoalveolar lavage fluid but represent a significant proportion of cells in digested lung tissue. Exclusion of IV leukocytes significantly improved the accuracy of the assessments of myeloid cells in the lung tissue and provided important insights into ongoing trafficking in both eosinophilic and neutrophilic asthma models.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815111","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

Scientific Articulation during Collaborative Digital Game-Based Learning Enhances Learning of Immunology. 基于数字游戏的协作学习中的科学表达增强了免疫学的学习。

ImmunoHorizons Pub Date : 2023-11-01 DOI: 10.4049/immunohorizons.2300004

Pey-Yng Low, Gaik-Bee Lim

{"title":"Scientific Articulation during Collaborative Digital Game-Based Learning Enhances Learning of Immunology.","authors":"Pey-Yng Low, Gaik-Bee Lim","doi":"10.4049/immunohorizons.2300004","DOIUrl":"10.4049/immunohorizons.2300004","url":null,"abstract":"Digital game-based learning has been used to help learners grasp complex concepts in science subjects such as immunology. The aim of this study was to examine whether playing a digital game collaboratively would encourage articulation of scientific terminology and concepts, and whether this would result in learning gains. Forty-seven students at a tertiary institution (17-19 y of age) played a game (n = 22) or watched a video of the game (n = 25) in small groups. This was followed by an activity to document the key learning points. Pretest and posttest results showed that although both groups had learning gains, the game-based learning group outperformed the video group for gains in procedural knowledge, suggesting that playing the game helped students to better internalize the steps involved in the immune response. For the game-based learning group, there was a positive correlation between the number of scientific terms articulated and the gains in the test scores. However, for the video group, there was no correlation. The implications for designing digital game-based learning activities for learning are discussed. The study was carried out in an online environment due to the COVID-19 pandemic mandating home-based learning at the time. The discussion also focuses on how the findings can be applied in an online and face-to-face context.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430509","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

Characterization of Canine Peyer's Patches by Multidimensional Analysis: Insights from Immunofluorescence, Flow Cytometry, and Single-Cell RNA Sequencing. 犬Peyer斑块的多维分析表征:来自免疫荧光、流式细胞术和单细胞RNA测序的见解。

ImmunoHorizons Pub Date : 2023-11-01 DOI: 10.4049/immunohorizons.2300091

Beatriz Miguelena Chamorro, Sodiq Ayobami Hameed, Marianne Dechelette, Jean-Baptiste Claude, Lauriane Piney, Ludivine Chapat, Gokul Swaminathan, Hervé Poulet, Stéphanie Longet, Karelle De Luca, Egbert Mundt, Stéphane Paul

{"title":"Characterization of Canine Peyer's Patches by Multidimensional Analysis: Insights from Immunofluorescence, Flow Cytometry, and Single-Cell RNA Sequencing.","authors":"Beatriz Miguelena Chamorro, Sodiq Ayobami Hameed, Marianne Dechelette, Jean-Baptiste Claude, Lauriane Piney, Ludivine Chapat, Gokul Swaminathan, Hervé Poulet, Stéphanie Longet, Karelle De Luca, Egbert Mundt, Stéphane Paul","doi":"10.4049/immunohorizons.2300091","DOIUrl":"10.4049/immunohorizons.2300091","url":null,"abstract":"The oral route is effective and convenient for vaccine administration to stimulate a protective immune response. GALT plays a crucial role in mucosal immune responses, with Peyer's patches (PPs) serving as the primary site of induction. A comprehensive understanding of the structures and functions of these structures is crucial for enhancing vaccination strategies and comprehending disease mechanisms; nonetheless, our current knowledge of these structures in dogs remains incomplete. We performed immunofluorescence and flow cytometry studies on canine PPs to identify cell populations and structures. We also performed single-cell RNA sequencing (scRNA-seq) to investigate the immune cell subpopulations present in PPs at steady state in dogs. We generated and validated an Ab specifically targeting canine M cells, which will be a valuable tool for elucidating Ag trafficking into the GALT of dogs. Our findings will pave the way for future studies of canine mucosal immune responses to oral vaccination and enteropathies. Moreover, they add to the growing body of knowledge in canine immunology, further expanding our understanding of the complex immune system of dogs.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138447570","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

Both Horatio and Polonius: Innate Lymphoid Cells in Tissue Homeostasis and Repair. Horatio和Polonius：组织稳态和修复中的固有淋巴细胞。

ImmunoHorizons Pub Date : 2023-11-01 DOI: 10.4049/immunohorizons.2300053

Intelly S Lee, Steven J Van Dyken

引用次数: 0

New Insights into the Complement Receptor of the Ig Superfamily Obtained from Structural and Functional Studies on Two Mutants. 从两个突变体的结构和功能研究获得Ig超家族补体受体的新见解

ImmunoHorizons Pub Date : 2023-11-01 DOI: 10.4049/immunohorizons.2300064

Huiquan Duan, Troy G Abram, Ana Rita Cruz, Suzan H M Rooijakkers, Brian V Geisbrecht

{"title":"New Insights into the Complement Receptor of the Ig Superfamily Obtained from Structural and Functional Studies on Two Mutants.","authors":"Huiquan Duan, Troy G Abram, Ana Rita Cruz, Suzan H M Rooijakkers, Brian V Geisbrecht","doi":"10.4049/immunohorizons.2300064","DOIUrl":"10.4049/immunohorizons.2300064","url":null,"abstract":"The extracellular region of the complement receptor of the Ig superfamily (CRIg) binds to certain C3 cleavage products (C3b, iC3b, C3c) and inhibits the alternative pathway (AP) of complement. In this study, we provide further insight into the CRIg protein and describe two CRIg mutants that lack multiple lysine residues as a means of facilitating chemical modifications of the protein. Structural analyses confirmed preservation of the native CRIg architecture in both mutants. In contrast to earlier reports suggesting that CRIg binds to C3b with an affinity of ∼1 μM, we found that wild-type CRIg binds to C3b and iC3b with affinities <100 nM, but to C3c with an affinity closer to 1 μM. We observed this same trend for both lysine substitution mutants, albeit with an apparent ∼2- to 3-fold loss of affinity when compared with wild-type CRIg. Using flow cytometry, we confirmed binding to C3 fragment-opsonized Staphylococcus aureus cells by each mutant, again with an ∼2- to 3-fold decrease when compared with wild-type. Whereas wild-type CRIg inhibits AP-driven lysis of rabbit erythrocytes with an IC50 of 1.6 μM, we observed an ∼3-fold reduction in inhibition for both mutants. Interestingly, we found that amine-reactive crosslinking of the CRIg mutant containing only a single lysine results in a significant improvement in inhibitory potency across all concentrations examined when compared with the unmodified mutant, but in a manner sensitive to the length of the crosslinker. Collectively, our findings provide new insights into the CRIg protein and suggest an approach for engineering increasingly potent CRIg-based inhibitors of the AP.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465207","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

BHLHE40 Mediates Cross-Talk between Pathogenic TH17 Cells and Myeloid Cells during Experimental Autoimmune Encephalomyelitis. BHLHE40介导实验性自身免疫性脑脊髓炎期间致病性TH17细胞和骨髓细胞之间的串扰。

ImmunoHorizons Pub Date : 2023-11-01 DOI: 10.4049/immunohorizons.2300042

Melissa E Cook, Irina Shchukina, Chih-Chung Lin, Tara R Bradstreet, Elizabeth A Schwarzkopf, Nicholas N Jarjour, Ashlee M Webber, Konstantin Zaitsev, Maxim N Artyomov, Brian T Edelson

{"title":"BHLHE40 Mediates Cross-Talk between Pathogenic TH17 Cells and Myeloid Cells during Experimental Autoimmune Encephalomyelitis.","authors":"Melissa E Cook, Irina Shchukina, Chih-Chung Lin, Tara R Bradstreet, Elizabeth A Schwarzkopf, Nicholas N Jarjour, Ashlee M Webber, Konstantin Zaitsev, Maxim N Artyomov, Brian T Edelson","doi":"10.4049/immunohorizons.2300042","DOIUrl":"10.4049/immunohorizons.2300042","url":null,"abstract":"TH17 cells are implicated in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). We previously reported that the transcription factor basic helix-loop-helix family member e40 (BHLHE40) marks cytokine-producing pathogenic TH cells during EAE, and that its expression in T cells is required for clinical disease. In this study, using dual reporter mice, we show BHLHE40 expression within TH1/17 and ex-TH17 cells following EAE induction. Il17a-Cre-mediated deletion of BHLHE40 in TH cells led to less severe EAE with reduced TH cell cytokine production. Characterization of the leukocytes in the CNS during EAE by single-cell RNA sequencing identified differences in the infiltrating myeloid cells when BHLHE40 was present or absent in TH17 cells. Our studies highlight the importance of BHLHE40 in promoting TH17 cell encephalitogenicity and instructing myeloid cell responses during active EAE.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490443","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

CD45.1/CD45.2 Congenic Markers Induce a Selective Bias for CD8+ T Cells during Adoptive Lymphocyte Reconstitution in Lymphocytopenia Mice. CD45.1/CD45.2同源标记物在淋巴细胞减少症小鼠过继性淋巴细胞重建过程中诱导CD8+T细胞的选择性偏向。

ImmunoHorizons Pub Date : 2023-11-01 DOI: 10.4049/immunohorizons.2300014

Rakhee Rathnam Kalari Kandy, Xiaoxuan Fan, Xuefang Cao

{"title":"CD45.1/CD45.2 Congenic Markers Induce a Selective Bias for CD8+ T Cells during Adoptive Lymphocyte Reconstitution in Lymphocytopenia Mice.","authors":"Rakhee Rathnam Kalari Kandy, Xiaoxuan Fan, Xuefang Cao","doi":"10.4049/immunohorizons.2300014","DOIUrl":"10.4049/immunohorizons.2300014","url":null,"abstract":"CD45.1/CD45.2 congenic markers have been used to track hematopoietic lineage differentiation following hematopoietic stem and progenitor cell (HSPC) transplantation. However, several studies suggest that a bias exists in CD45.1 versus CD45.2 hematopoietic cell reconstitution from HSPCs. Meanwhile, no definitive comparison has been reported for mature immune cells as to whether the CD45.1/CD45.2 disparity can skew the immune cell response. In this study, using lymphocytopenia Rag1-/- CD45.2 mice as hosts, we assessed the reconstitution potential of CD45.1 versus CD45.2 lymphocytes following adoptive transfer of mature T and B cells. We have found a selective bias for CD8+ T cells in that CD45.1 cells showed significantly higher reconstitution compared with CD45.2 cells, whereas CD4+ T cells and CD19+ B cells showed equivalent reconstitution. These results suggest that CD45.1/CD45.2 markers may induce an alloreactive response or a survival bias specific to CD8+ T cells, and they therefore call for caution for using them as congenic markers in immunologic models.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490444","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

STAT3 Signaling Heterogeneity Underlies Cytokine-Expressing Fate in Th17 Cultures. STAT3信号的异质性是Th17培养物中细胞因子表达命运的基础。

ImmunoHorizons Pub Date : 2023-11-01 DOI: 10.4049/immunohorizons.2300072

Michelle L Niese, Nicole Glosson-Byers, Ana Paula Moreira Serezani, Nada S Alakhras, Mark H Kaplan

{"title":"STAT3 Signaling Heterogeneity Underlies Cytokine-Expressing Fate in Th17 Cultures.","authors":"Michelle L Niese, Nicole Glosson-Byers, Ana Paula Moreira Serezani, Nada S Alakhras, Mark H Kaplan","doi":"10.4049/immunohorizons.2300072","DOIUrl":"10.4049/immunohorizons.2300072","url":null,"abstract":"The polarization of naive Th cells into differentiated subsets in vitro was a powerful approach to define the development and function of Th cells in vivo. Th cell cultures identified cytokines that promote polarization and defined the phenotype and stability of differentiated cells. One of the limitations of this approach is the heterogeneity of the differentiated culture, essentially with regard to what proportion of the culture is secreting the hallmark cytokine of interest. This heterogeneity has always been puzzling because all cells in the culture have been exposed to identical culture conditions. We examined this phenomenon using an Il17f lineage-tracing allele (Cost, Cre on seventeen transcript) crossed to stop-flox Rosa-YFP (yellow fluorescent protein) mice. We found that less than half of the cells in a Th17 culture become lineage-positive during a differentiation culture and that it is primarily cells that are lineage-positive that produce cytokines when cultures are restimulated after differentiation. We sorted and analyzed YFP-positive and YFP-negative cells and found similar expression of many Th17 transcription factors, although YFP-negative cells had increased expression of other lineage-defining transcription factors. We observed that YFP-negative cells had diminished expression of Stat3 and Il6ra, as well as decreased STAT3 activation. YFP-negative cells transduced with active STAT3 had significant increases in IL-17A expression, without increases in Th17 transcription factors. Taken together, these data suggest that there is a threshold of STAT3 activation that is required for efficient Th17 differentiation, and that even in a culture of homogeneous naive T cells there is heterogeneity in the receipt of early cytokine signals.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490445","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