Regulatory T cells (Tregs) contribute to skin homeostasis, but the antigenic targets remain unclear. The infiltration of Tregs is coincident with CD1a-expressing cells during skin inflammation, and whilst CD1a is known to present lipid antigens to effector T cells, the extent to which CD1a presents lipid antigens to Tregs has not been investigated. Here, we show CD1a reactivity in subsets of human circulating and cutaneous CD4+ Tregs, displaying ab T cell receptors (TCRs), memory phenotypes and suppressive functions, including the ability to secrete interleukin-10 (IL-10) in response to the permissive lipid antigen lysophosphatidylcholine, known to be enriched in skin inflammation. Next, single-cell CITE-seq analyses of CD1a-reactive IL-10–producing CD4+ Tregs from psoriatics showed maintenance of some canonical characteristics including LAG-3+CD49b+ expression, but with altered pro-inflammatory signatures including up-regulated type 1 and 17 effector function. In addition, clonally expanded IL-10–producing Tregs retained their suppressive phenotype in a CD1a- and TCR-dependent manner. Together, these findings show that subsets of Tregs are directed to self-lipid antigens and CD1a, but show an altered phenotype equipped with pro-inflammatory potential in the setting of psoriasis.