@article{3d4e486ef3b042ab9a8ba444d7d3bfe4,
title = "TREM2 macrophages induced by human lipids drive inflammation in acne lesions",
abstract = "Acne affects 1 in 10 people globally, often resulting in disfigurement. The disease involves excess production of lipids, particularly squalene, increased growth of Cutibacterium acnes, and a host inflammatory response with foamy macrophages. By combining single-cell and spatial RNA sequencing as well as ultrahigh-resolution Seq-Scope analyses of early acne lesions on back skin, we identified TREM2 macrophages expressing lipid metabolism and proinflammatory gene programs in proximity to hair follicle epithelium expressing squalene epoxidase. We established that the addition of squalene induced differentiation of TREM2 macrophages in vitro, which were unable to kill C. acnes. The addition of squalene to macrophages inhibited induction of oxidative enzymes and scavenged oxygen free radicals, providing an explanation for the efficacy of topical benzoyl peroxide in the clinical treatment of acne. The present work has elucidated the mechanisms by which TREM2 macrophages and unsaturated lipids, similar to their involvement in atherosclerosis, may contribute to the pathogenesis of acne.",
author = "Do, {Tran H.} and Feiyang Ma and Andrade, {Priscila R.} and Rosane Teles and {de Andrade Silva}, {Bruno J.} and Chanyue Hu and Alejandro Espinoza and Hsu, {Jer En} and Cho, {Chun Seok} and Myungjin Kim and Jingyue Xi and Xianying Xing and Olesya Plazyo and Tsoi, {Lam C.} and Carol Cheng and Jenny Kim and Bryson, {Bryan D.} and O{\textquoteright}Neill, {Alan M.} and Marco Colonna and Gudjonsson, {Johann E.} and Eynav Klechevsky and Lee, {Jun Hee} and Gallo, {Richard L.} and Bloom, {Barry R.} and Matteo Pellegrini and Modlin, {Robert L.}",
note = "Funding Information: T.H.D. is supported by NIH T32-GM008042 and NIH T32-AT071307. R.L.G. and R.L.M. are supported by NIH R01-AR074302. J.-E.H. is supported by a Taiwan Government Scholarship. J.H.L. is supported by a Michigan Translational Research and Commercialization (MTRAC) award and NIH UG3-CA268091. C.-S.C. is supported by NIH T32-AG000114. M.K. is supported by NIH K01-AG061236. J.E.G. and L.C.T. are supported by NIH P30-AR075043, and the Taubman Medical Research Institute (to J.E.G.). E.K. is supported by NIH R01-AR075959-01 and NIH R01-CA245277. Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved.",
year = "2022",
month = jul,
doi = "10.1126/sciimmunol.abo2787",
language = "English",
volume = "7",
journal = "Science immunology",
issn = "2470-9468",
number = "73",
}