| First Author | Sivasami P | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 8 | Pages | 1844-1861.e6 |
| PubMed ID | 37478855 | Mgi Jnum | J:341067 |
| Mgi Id | MGI:7519972 | Doi | 10.1016/j.immuni.2023.06.021 |
| Citation | Sivasami P, et al. (2023) Obesity-induced dysregulation of skin-resident PPARgamma(+) Treg cells promotes IL-17A-mediated psoriatic inflammation. Immunity 56(8):1844-1861.e6 |
| abstractText | Obesity is a major risk factor for psoriasis, but how obesity disrupts the regulatory mechanisms that keep skin inflammation in check is unclear. Here, we found that skin was enriched with a unique population of CD4(+)Foxp3(+) regulatory T (Treg) cells expressing the nuclear receptor peroxisome proliferation-activated receptor gamma (PPARgamma). PPARgamma drove a distinctive transcriptional program and functional suppression of IL-17A(+) gammadelta T cell-mediated psoriatic inflammation. Diet-induced obesity, however, resulted in a reduction of PPARgamma(+) skin Treg cells and a corresponding loss of control over IL-17A(+) gammadelta T cell-mediated inflammation. Mechanistically, PPARgamma(+) skin Treg cells preferentially took up elevated levels of long-chain free fatty acids in obese mice, which led to cellular lipotoxicity, oxidative stress, and mitochondrial dysfunction. Harnessing the anti-inflammatory properties of these PPARgamma(+) skin Treg cells could have therapeutic potential for obesity-associated inflammatory skin diseases. |
