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We report here these mice also exhibit acquired lipodystrophy, hepatic steatosis, and insulin resistance. Adipose tissue exhibited lymphocytic infiltration followed by CD8+ T cell\u2013mediated destruction of adipocytes. Helios-deficient Tregs were more frequent in adipose tissue and showed an enhanced effector Treg (eTreg) phenotype (CD62Llo Tcf1lo). The Helios-deficient eTregs in adipose tissue, but not spleen, failed to develop into terminally differentiated eTregs, which express ST2+, CXCR3+, IRF4, or Klrg1+. ChIP-seq studies demonstrated that Helios bound to regulatory elements in multiple genes (Tcf7, Lef1, Bach2, and Id3) known to restrict eTreg generation. Thus, Helios not only directly restricts eTreg generation but also indirectly enforces functional eTreg differentiation. In the absence of Helios, the process of eTreg differentiation proceeds unchecked, resulting in enhanced but dysfunctional eTregs, which fail to control adipose tissue homeostasis.<\/jats:p>","DOI":"10.1084\/jem.20260870","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:20:56Z","timestamp":1789021256000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Helios is critical for Treg effector differentiation in adipose autoimmunity"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4175-4154","authenticated-orcid":true,"given":"Angela M.","family":"Thornton","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health 1 Cellular Immunology Section, Laboratory of Immune System Biology, , 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