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However, it is not known how these microbiota-driven immune responses are regulated. Here, we report that depletion of Foxp3+ regulatory T cells (Tregs) in Staphylococcus aureus\u2013colonized mice resulted in less IL-17 and an IFN-\u03b3\u2013dependent skin inflammation with impaired S. aureus immunity. Similarly, reducing Tregs in S. aureus\u2013colonized and Leishmania braziliensis\u2013infected mice increased IFN-\u03b3, S. aureus, and disease severity. Importantly, analysis of lesions from L. braziliensis patients revealed that low FOXP3 gene expression is associated with high IFNG expression, S. aureus burden, and delayed lesion resolution compared to patients with high FOXP3 expression. Thus, we found a critical role for Tregs in regulating the balance between IL-17 and IFN-\u03b3 in the skin, which influences both bacterial burden and disease. These results have clinical ramifications for cutaneous leishmaniasis and other skin diseases associated with a dysregulated microbiome when Tregs are limited or dysfunctional.<\/jats:p>","DOI":"10.1084\/jem.20230558","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T02:20:58Z","timestamp":1695176458000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Regulatory T cells control\n                    <i>Staphylococcus aureus<\/i>\n                    and disease severity of cutaneous leishmaniasis"],"prefix":"10.1084","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0122-1089","authenticated-orcid":true,"given":"Tej Pratap","family":"Singh","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Veterinary Medicine, University of Pennsylvania 1 Department of Pathobiology, , 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