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The precise mechanisms by which Treg cells mediate such functions have extensively been explored, and there are many cellular and molecular factors that are instrumental for adequate Treg cell functions. microRNAs, small noncoding RNA molecules, are one of the factors capable of regulating Treg cell functions. In this study, we report that miR-342 is essential for Treg cells to mitigate autoimmune inflammation in the central nervous system and allergic airway inflammation in the lung. Utilizing novel mouse models with Treg cell\u2013specific miR-342 deficiency or overexpression, we demonstrate that miR-342 expression in Treg cells, while dispensable for immune homeostasis at steady-state conditions, is necessary for Treg cells to control inflammatory responses. Mechanistically, we found that Treg cells deficient in miR-342 display dysregulated metabolic profiles, elevated glycolysis and decreased oxidative phosphorylation, a metabolic phenotype associated with functionally defective Treg cells. Interestingly, miR-342\u2013dependent metabolic dysregulation was observed in Treg but not in T helper 1\u2013type cells. In support, miR-342\u2013mediated Rictor targeting was found in Treg but not in T helper 1\u2013type cells. Last, Treg cells overexpressing miR-342 were able to effectively suppress ongoing autoimmune inflammation in an adoptive Treg transfer but not in active disease model. Collectively, our findings uncover that miR-342 may serve a key regulator specific for metabolism and functions in Treg cells.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf181","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T18:26:11Z","timestamp":1755023171000},"page":"2976-2986","source":"Crossref","is-referenced-by-count":2,"title":["Intronic miR-342 is a key regulator of cellular glycolysis in Foxp3+ regulatory CD4 T cells"],"prefix":"10.1093","volume":"214","author":[{"given":"Rongzhen","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine , Chicago, IL 60611,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine , Chicago, IL 60611,","place":["United 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