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
Affiliations
Micha L. Davila
Immunology and Infectious Disease Graduate Program, The Pennsylvania State University, University Park, PA 16802, USA; 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
Ming Xu
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
Chengyu Huang
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
Erin R. Gaddes
Department of Biomedical Engineering, 526 CBEB, The Pennsylvania State University, University Park, PA 16802, USA
Levi Winter
Pathobiology Graduate Program, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA
Margherita T. Cantorna
Pathobiology Graduate Program, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA
Yong Wang
Department of Biomedical Engineering, 526 CBEB, The Pennsylvania State University, University Park, PA 16802, USA
Na Xiong
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; 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; Corresponding author
Summary: 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.
