摘要:SummaryAbundant 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.Graphical abstractDisplay OmittedHighlights•The creation of a line of total CCL27-knockout (KO) mice•CCL27-KO mice are impaired in establishment of skin-resident Treg and Teff cells•Imiquimod-treated CCL27-KO mice have increased skin IL-17+T cells and inflammation•CCL27-KO mice have impaired T cell homeostasis in lungs and reproductive tractsBiological sciences; Immunology; Immune response