CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues

Micha L Davila; Ming Xu; Chengyu Huang; Erin R Gaddes; Levi Winter; Margherita T Cantorna; Yong Wang; Na Xiong

doi:10.1016/j.isci.2022.104426

CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues

iScience. 2022 May 18;25(6):104426. doi: 10.1016/j.isci.2022.104426. eCollection 2022 Jun 17.

Authors

Micha L Davila^{1

2}, Ming Xu², Chengyu Huang², Erin R Gaddes³, Levi Winter⁴, Margherita T Cantorna⁴, Yong Wang³, Na Xiong^{2

5}

Affiliations

¹ Immunology and Infectious Disease Graduate Program, The Pennsylvania State University, University Park, PA 16802, USA.
² Department of Microbiology, Immunology and Molecular Genetics, Joe R. & Teresa Lozano Long School of Medicine, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, Mail Code 7758, San Antonio, TX 78229, USA.
³ Department of Biomedical Engineering, 526 CBEB, The Pennsylvania State University, University Park, PA 16802, USA.
⁴ Pathobiology Graduate Program, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
⁵ Department of Medicine-Division of Dermatology and Cutaneous Surgery University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.

Abstract

Abundant immune cells reside in barrier tissues. Understanding the regulation of these cells can yield insights on their roles in tissue homeostasis and inflammation. Here, we report that the chemokine CCL27 is critical for establishment of resident lymphocytes and immune homeostasis in barrier tissues. CCL27 expression is associated with normal skin and hair follicle development independent of commensal bacterial stimulation, indicative of a homeostatic role for the chemokine. Accordingly, in the skin of CCL27-knockout mice, there is a reduced presence and dysregulated localization of T cells that express CCR10, the cognate receptor to CCL27. Besides, CCL27-knockout mice have overreactive skin inflammatory responses in an imiquimod-induced model of psoriasis. Beyond the skin, CCL27-knockout mice have increased infiltration of CCR10⁺ T cells into lungs and reproductive tracts, the latter of which also exhibit spontaneous inflammation. Our findings demonstrate that CCL27 is critical for immune homeostasis across barrier tissues.

Keywords: Biological sciences; Immune response; Immunology.

Abstract

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