TREM2 macrophages induced by human lipids drive inflammation in acne lesions.
IF: 30.630
Cited by: 17


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.



MeSH terms

Acne Vulgaris
Membrane Glycoproteins
Receptors, Immunologic


Do, Tran H
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