ImmunoHorizonsPub Date : 2023-12-01DOI: 10.4049/immunohorizons.2300090
Bonnie J Lafleur, Lisa White, Michael D Dake, Janko Z Nikolich, Ryan Sprissler, Deepta Bhattacharya
{"title":"No Evidence That Analgesic Use after COVID-19 Vaccination Negatively Impacts Antibody Responses.","authors":"Bonnie J Lafleur, Lisa White, Michael D Dake, Janko Z Nikolich, Ryan Sprissler, Deepta Bhattacharya","doi":"10.4049/immunohorizons.2300090","DOIUrl":"10.4049/immunohorizons.2300090","url":null,"abstract":"<p><p>Uptake of mRNA vaccines, especially booster immunizations, against COVID-19 has been lower than hoped, perhaps in part due to their reactogenicity. Analgesics might alleviate symptoms associated with vaccination, but they might also impact immune responses. We semiquantitatively measured Ab responses following COVID-19 vaccination in 2354 human participants surveyed about analgesic use after vaccination. Participants who used nonsteroidal anti-inflammatory drugs or acetaminophen after vaccination showed elevated Ab levels against the receptor-binding domain of Spike protein relative to those who did not use analgesics. This pattern was observed for both mRNA-1273 and BNT162b2 and across age groups. Participants who used analgesics more frequently reported fatigue, muscle aches, and headaches than did those who did not use painkillers. Among participants who reported these symptoms, we observed no statistically significant differences in Ab levels irrespective of analgesic use. These data suggest that elevated Ab levels are associated with symptoms and inflammatory processes rather than painkiller use per se. Taken together, we find no evidence that analgesic use reduces Ab responses after COVID-19 vaccination. Recommendation of their use to alleviate symptoms might improve uptake of booster immunizations.</p>","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/PMC10759157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815116","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}
ImmunoHorizonsPub Date : 2023-12-01DOI: 10.4049/immunohorizons.2300061
Heather L Caslin, W Reid Bolus, Christopher Thomas, Shinji Toki, Allison E Norlander, R Stokes Peebles, Alyssa H Hasty
{"title":"Bovine Serum Albumin Elicits IL-33-Dependent Adipose Tissue Eosinophilia: Potential Relevance to Ovalbumin-induced Models of Allergic Disease.","authors":"Heather L Caslin, W Reid Bolus, Christopher Thomas, Shinji Toki, Allison E Norlander, R Stokes Peebles, Alyssa H Hasty","doi":"10.4049/immunohorizons.2300061","DOIUrl":"10.4049/immunohorizons.2300061","url":null,"abstract":"<p><p>All cells of the immune system reside in adipose tissue (AT), and increasing type 2 immune cells may be a therapeutic strategy to improve metabolic health. In our previous study using i.p. IL-5 injections to increase eosinophils, we observed that a standard vehicle control of 0.1% BSA also elicited profound AT eosinophilia. In this study, we aimed to determine whether BSA-induced AT eosinophilia results in metabolic benefits in murine models of diet-induced obesity. I.p. 0.1% BSA injections increased AT eosinophils after 4 wk. Despite elevating eosinophils to >50% of immune cells in the AT, body weight and glucose tolerance were not different between groups. Interestingly, BSA elicited epithelial IL-33 production, as well as gene expression for type 2 cytokines and IgE production that were dependent on IL-33. Moreover, multiple models of OVA sensitization also drove AT eosinophilia. Following transplantation of a donor fat pad with BSA-induced eosinophilia, OVA-sensitized recipient mice had higher numbers of bronchoalveolar lavage eosinophils that were recipient derived. Interestingly, lungs of recipient mice contained eosinophils, macrophages, and CD8 T cells from the donor AT. These trafficked similarly from BSA- and non-BSA-treated AT, suggesting even otherwise healthy AT serves as a reservoir of immune cells capable of migrating to the lungs. In conclusion, our studies suggest that i.p. injections of BSA and OVA induce an allergic response in the AT that elicits eosinophil recruitment, which may be an important consideration for those using OVA in animal models of allergic disease.</p>","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/PMC10759155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815108","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}
ImmunoHorizonsPub Date : 2023-12-01DOI: 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":"<p><p>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.</p>","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}
ImmunoHorizonsPub Date : 2023-12-01DOI: 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":"<p><p>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.</p>","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}
ImmunoHorizonsPub Date : 2023-12-01DOI: 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":"<p><p>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.</p>","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}
ImmunoHorizonsPub Date : 2023-11-01DOI: 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":"<p><p>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.</p>","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}
{"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":"<p><p>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.</p>","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}
ImmunoHorizonsPub Date : 2023-11-01DOI: 10.4049/immunohorizons.2300053
Intelly S Lee, Steven J Van Dyken
{"title":"Both Horatio and Polonius: Innate Lymphoid Cells in Tissue Homeostasis and Repair.","authors":"Intelly S Lee, Steven J Van Dyken","doi":"10.4049/immunohorizons.2300053","DOIUrl":"10.4049/immunohorizons.2300053","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) have emerged as critical tissue-resident lymphocytes that coordinate responses to environmental stress and injury. Traditionally, their function was thought to mirror adaptive lymphocytes that respond to specific pathogens. However, recent work has uncovered a more central role for ILCs in maintaining homeostasis even in the absence of infection. ILCs are now better conceptualized as an environmental rheostat that helps maintain the local tissue setpoint during environmental challenge by integrating sensory stimuli to direct homeostatic barrier and repair programs. In this article, we trace the developmental origins of ILCs, relate how ILCs sense danger signals, and describe their subsequent engagement of appropriate repair responses using a general paradigm of ILCs functioning as central controllers in tissue circuits. We propose that these interactions form the basis for how ILC subsets maintain organ function and organismal homeostasis, with important implications for human health.</p>","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/PMC10695417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430508","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}
ImmunoHorizonsPub Date : 2023-11-01DOI: 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":"<p><p>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.</p>","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}
ImmunoHorizonsPub Date : 2023-11-01DOI: 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":"<p><p>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.</p>","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}