TREM2 macrophages induced by human lipids drive inflammation in acne lesions-Reference-Cited by-同舟云学术

TREM2 macrophages induced by human lipids drive inflammation in acne lesions

Published:2022-07-22 Issue:73 Volume:7 Page:
ISSN:2470-9468
Container-title:Science Immunology
language:en
Short-container-title:Sci. Immunol.

Author:

Do Tran H.¹²^ORCID,Ma Feiyang¹³^ORCID,Andrade Priscila R.²,Teles Rosane²^ORCID,de Andrade Silva Bruno J.²^ORCID,Hu Chanyue³⁴^ORCID,Espinoza Alejandro³⁴^ORCID,Hsu Jer-En⁵,Cho Chun-Seok⁵^ORCID,Kim Myungjin⁵,Xi Jingyue⁶,Xing Xianying⁷^ORCID,Plazyo Olesya⁷^ORCID,Tsoi Lam C.⁷^ORCID,Cheng Carol²,Kim Jenny²,Bryson Bryan D.⁸^ORCID,O’Neill Alan M.⁹^ORCID,Colonna Marco¹⁰^ORCID,Gudjonsson Johann E.⁷^ORCID,Klechevsky Eynav¹⁰^ORCID,Lee Jun Hee⁵^ORCID,Gallo Richard L.⁹^ORCID,Bloom Barry R.¹¹^ORCID,Pellegrini Matteo³⁴^ORCID,Modlin Robert L.²¹²^ORCID

Affiliation:

1. Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

2. Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles,, Los Angeles, CA 90095, USA.

3. Institute for Quantitative and Computational Biosciences—The Collaboratory, University of California, Los Angeles, Los Angeles, CA 90095, USA.

4. Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

5. Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

6. Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

7. Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.

8. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

9. Department of Dermatology, University of California San Diego, La Jolla, CA 92093, USA.

10. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

11. Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

12. Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

Acne affects 1 in 10 people globally, often resulting in disfigurement. The disease involves excess production of lipids, particularly squalene, increased growth ofCutibacterium 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 killC. 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine,Immunology

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