{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:36:50Z","timestamp":1782484610512,"version":"3.54.5"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Mucosal-associated invariant T (MAIT) cells are innate-like T cells that develop in the thymus through three maturation stages to acquire effector function and differentiate into MAIT1 (T-bet<jats:sup>+<\/jats:sup>) and MAIT17 (ROR\u03b3t<jats:sup>+<\/jats:sup>) subsets. Upon activation, MAIT cells release IFN-\u03b3 and IL-17, which modulate a broad spectrum of diseases. Recent studies indicate defective MAIT cell development in microRNA deficient mice, however, few individual miRNAs have been identified to regulate MAIT cells. MicroRNA-155 (miR-155) is a key regulator of numerous cellular processes that affect some immune cell development, but its role in MAIT cell development remains unclear. To address whether miR-155 is required for MAIT cell development, we performed gain-of-function and loss-of-function studies. We first generated a CD4Cre.miR-155 knock-in mouse model, in which miR-155 is over-expressed in the T cell lineage. We found that overexpression of miR-155 significantly reduced numbers and frequencies of MAIT cells in all immune organs and lungs and blocked thymic MAIT cell maturation through downregulating PLZF expression. Strikingly, upregulated miR-155 promoted MAIT1 differentiation and blocked MAIT17 differentiation, and timely inducible expression of miR-155 functionally inhibited peripheral MAIT cells secreting IL-17. miR-155 overexpression also increased CD4<jats:sup>\u2013<\/jats:sup>CD8<jats:sup>+<\/jats:sup> subset and decreased CD4<jats:sup>\u2013<\/jats:sup>CD8<jats:sup>\u2013<\/jats:sup> subset of MAIT cells. We further analyzed MAIT cells in conventional miR-155 knockout mice and found that lack of miR-155 also promoted MAIT1 differentiation and blocked MAIT17 differentiation but without alteration of their overall frequency, maturation and function. Overall, our results indicate that adequate miR-155 expression is required for normal MAIT1 and MAIT17 cell development and function.<\/jats:p>","DOI":"10.3389\/fcell.2021.670531","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T07:17:14Z","timestamp":1617952634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["MicroRNA-155 Regulates MAIT1 and MAIT17 Cell Differentiation"],"prefix":"10.3389","volume":"9","author":[{"given":"Tingting","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana","family":"Subedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijun","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Sheng","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: genomics, biogenesis, mechanism, and function.","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"14","DOI":"10.4049\/immunohorizons.1900061","article-title":"Inflammatory cytokines induce sustained CTLA-4 cell surface expression on human MAIT Cells.","volume":"4","author":"Berkson","year":"2020","journal-title":"Immunohorizons"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00140","article-title":"Regulated expression of miR-155 is required for iNKT cell development.","volume":"6","author":"Burocchi","year":"2015","journal-title":"Front. 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