{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:09:00Z","timestamp":1788786540487,"version":"build-2803163510"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health","award":["DK135193"],"award-info":[{"award-number":["DK135193"]}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health","award":["DK112436"],"award-info":[{"award-number":["DK112436"]}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health","award":["DK125011"],"award-info":[{"award-number":["DK125011"]}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health","award":["DK124132"],"award-info":[{"award-number":["DK124132"]}]},{"DOI":"10.13039\/100011684","name":"Crohn\u2019s & Colitis Foundation","doi-asserted-by":"crossref","award":["1005605"],"award-info":[{"award-number":["1005605"]}],"id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interleukin 22 (IL-22) produced by CD4+ T cells plays an important role in regulating intestinal immune responses during inflammation and infection, but the mechanisms controlling IL-22 expression in T cells remain incompletely understood. MicroRNA-10a (miR-10a) is known to regulate CD4+ T-cell function, but its role in IL-22 production has not been defined. Here, using mouse CD4+ T cell\u2013specific miR-10a knockout models, we examined how miR-10a regulates IL-22 expression and the underlying metabolic mechanisms. MiR-10a deficiency led to increased IL-22 production in CD4+ T cells both in vitro and in vivo, under steady and inflammatory conditions. CD4+ T cell\u2013specific miR-10a knockout mice were resistant to Citrobacter rodentium infection, and the protection was abolished when blocking the IL-22 pathway in mice. Mechanistically, miR-10a\u2013deficient CD4+ T cells exhibited increased mitochondrial oxidative metabolism and membrane potential. Pharmacologic inhibition of mitochondrial complex III with antimycin A suppressed the enhanced IL-22 production in miR-10a\u2013deficient T cells. We further identified Uqcrq, a subunit of mitochondrial complex III, as a direct target of miR-10a, and loss of Uqcrq suppressed IL-22 production in CD4+ T cells. Together, these findings identify miR-10a as a T cell\u2013intrinsic regulator of mitochondrial oxidative metabolism that constrains IL-22 production in the intestine.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag089","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T19:38:19Z","timestamp":1777318699000},"source":"Crossref","is-referenced-by-count":0,"title":["Deficiency of microRNA-10a in CD4+ T cells protects against intestinal infection through mitochondrial oxidation\u2013IL-22 pathway"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1541-1892","authenticated-orcid":false,"given":"Wenjing","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]},{"name":"Center for Human Immunobiology, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianming","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]},{"name":"Center for Human Immunobiology, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suxia","family":"Yao","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]},{"name":"Center for Human Immunobiology, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"Cong","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]},{"name":"Center for Human Immunobiology, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]},{"name":"Department of Pathology, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]},{"name":"Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"2026090708221127700_vkag089-B1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.chom.2016.03.003","article-title":"Intrinsic defense mechanisms of the intestinal epithelium","volume":"19","author":"Ramanan","year":"2016","journal-title":"Cell Host Microbe"},{"key":"2026090708221127700_vkag089-B2","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1038\/s41467-020-18262-6","article-title":"Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity","volume":"11","author":"Yang","year":"2020","journal-title":"Nat Commun"},{"key":"2026090708221127700_vkag089-B3","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.immuni.2008.11.003","article-title":"Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease","volume":"29","author":"Zenewicz","year":"2008","journal-title":"Immunity"},{"key":"2026090708221127700_vkag089-B4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/cpt.1164","article-title":"Randomized phase I healthy volunteer study of UTTR1147A (IL-22Fc): a potential therapy for epithelial injury","volume":"105","author":"Rothenberg","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"2026090708221127700_vkag089-B5","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1136\/gutjnl-2014-307980","article-title":"miR-10a inhibits dendritic cell activation and Th1\/Th17 cell immune responses in IBD","volume":"64","author":"Wu","year":"2015","journal-title":"Gut"},{"key":"2026090708221127700_vkag089-B6","doi-asserted-by":"crossref","first-page":"e09953","DOI":"10.1002\/advs.202509953","article-title":"Intrinsic microRNA-10a restricts regulatory T cell suppressive function and intestinal repair by coordinating transcriptional, metabolic, and epithelial repair pathways","volume":"13","author":"Yang","year":"2026","journal-title":"Adv Sci (Weinh)."},{"key":"2026090708221127700_vkag089-B7","doi-asserted-by":"crossref","first-page":"985","DOI":"10.4049\/jimmunol.2100017","article-title":"MicroRNA-10a negatively regulates CD4(+) T cell IL-10 production through suppression of Blimp1","volume":"207","author":"Yang","year":"2021","journal-title":"J Immunol"},{"key":"2026090708221127700_vkag089-B8","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41423-024-01148-8","article-title":"Cellular metabolism regulates the differentiation and function of T-cell subsets","volume":"21","author":"Ma","year":"2024","journal-title":"Cell Mol Immunol"},{"key":"2026090708221127700_vkag089-B9","doi-asserted-by":"crossref","first-page":"pbac018","DOI":"10.1093\/pcmedi\/pbac018","article-title":"CD4+ T cell metabolism, gut microbiota, and autoimmune diseases: implication in precision medicine of autoimmune diseases","volume":"5","author":"Yang","year":"2022","journal-title":"Precis Clin Med"},{"key":"2026090708221127700_vkag089-B10","doi-asserted-by":"crossref","first-page":"101674","DOI":"10.1016\/j.redox.2020.101674","article-title":"Mitochondrial electron transport chain: oxidative phosphorylation, oxidant production, and methods of measurement","volume":"37","author":"Nolfi-Donegan","year":"2020","journal-title":"Redox Biol"},{"key":"2026090708221127700_vkag089-B11","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.ajhg.2008.03.020","article-title":"Mitochondrial complex III deficiency associated with a homozygous mutation in UQCRQ","volume":"82","author":"Barel","year":"2008","journal-title":"Am J Human Genet"},{"key":"2026090708221127700_vkag089-B12","first-page":"e63293","article-title":"Induction of intestinal inflammation by adoptive transfer of CBir1 TCR transgenic CD4+ T cells to immunodeficient mice","volume":"178","author":"Yang","year":"2021","journal-title":"J Vis Exp"},{"key":"2026090708221127700_vkag089-B13","first-page":"4557","article-title":"A guide to histomorphological evaluation of intestinal inflammation in mouse models","volume":"7","author":"Erben","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"2026090708221127700_vkag089-B14","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1053\/j.gastro.2021.09.018","article-title":"GPR120 inhibits colitis through regulation of CD4+ T cell interleukin 10 production","volume":"162","author":"Yang","year":"2022","journal-title":"Gastroenterology"},{"key":"2026090708221127700_vkag089-B15","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1038\/s41590-025-02257-w","article-title":"SATB1 is a key regulator of quiescence in stem-like CD8(+) T cells","volume":"26","author":"Lin","year":"2025","journal-title":"Nat Immunol"},{"key":"2026090708221127700_vkag089-B16","doi-asserted-by":"crossref","first-page":"11673","DOI":"10.1093\/nar\/gks901","article-title":"miRmap: comprehensive prediction of microRNA target repression strength","volume":"40","author":"Vejnar","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2026090708221127700_vkag089-B17","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.cyto.2008.11.010","article-title":"miRNA regulation of cytokine genes","volume":"45","author":"Asirvatham","year":"2009","journal-title":"Cytokine"},{"key":"2026090708221127700_vkag089-B18","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1002\/eji.201545487","article-title":"Cross-regulation between cytokine and microRNA pathways in T cells","volume":"45","author":"Amado","year":"2015","journal-title":"Eur J Immunol"},{"key":"2026090708221127700_vkag089-B19","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/ni.2286","article-title":"TGF-\u03b2 and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells","volume":"13","author":"Takahashi","year":"2012","journal-title":"Nat Immunol"},{"key":"2026090708221127700_vkag089-B20","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1084\/jem.20070104","article-title":"Interleukin-10 production by effector T cells: Th1 cells show self control","volume":"204","author":"Trinchieri","year":"2007","journal-title":"J Exp Med"},{"key":"2026090708221127700_vkag089-B21","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1038\/ni.1791","article-title":"Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis","volume":"10","author":"Murai","year":"2009","journal-title":"Nat Immunol"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/4\/vkag089\/68171599\/vkag089.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/4\/vkag089\/68171599\/vkag089.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:22:24Z","timestamp":1788783744000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/doi\/10.1093\/jimmun\/vkag089\/8663635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,15]]}},"URL":"https:\/\/doi.org\/10.1093\/jimmun\/vkag089","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,4]]},"article-number":"vkag089"}}