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TREM2 macrophages induced by human lipids drive inflammation in acne lesions

Title: TREM2 macrophages induced by human lipids drive inflammation in acne lesions
Authors: H, Tran; Ma, Feiyang; Andrade, Priscila R; Teles, Rosane; de Andrade Silva, Bruno J; Hu, Chanyue; Espinoza, Alejandro; Hsu, Jer-En; Cho, Chun-Seok; Kim, Myungjin; Xi, Jingyue; Xing, Xianying; Plazyo, Olesya; Tsoi, Lam C; Cheng, Carol; Kim, Jenny; Bryson, Bryan D; O’Neill, Alan M; Colonna, Marco; Gudjonsson, Johann E; Klechevsky, Eynav; Lee, Jun Hee; Gallo, Richard L; Bloom, Barry R; Pellegrini, Matteo; Modlin, Robert L
Source: Science Immunology, vol 7, iss 73
Publisher Information: eScholarship, University of California
Publication Year: 2022
Collection: University of California: eScholarship
Subject Terms: 32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); 3204 Immunology (for-2020); Clinical Research (rcdc); Human Genome (rcdc); Genetics (rcdc); Atherosclerosis (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); Acne Vulgaris (mesh); Humans (mesh); Inflammation (mesh); Lipids (mesh); Macrophages (mesh); Membrane Glycoproteins (mesh); Receptors; Immunologic (mesh); Squalene (mesh)
Subject Geographic: eabo2787 - eabo2787
Description: 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
Relation: qt2800q59v; https://escholarship.org/uc/item/2800q59v; https://escholarship.org/content/qt2800q59v/qt2800q59v.pdf
DOI: 10.1126/sciimmunol.abo2787
Availability: https://escholarship.org/uc/item/2800q59v; https://escholarship.org/content/qt2800q59v/qt2800q59v.pdf; https://doi.org/10.1126/sciimmunol.abo2787
Rights: public
Accession Number: edsbas.9D08DFCC
Database: BASE