The role of CCL27 in the establishment, maintenance, and homeostasis of skin-resident CCR10+ lymphocytes

Abstract

Abstract The skin hosts an array of immune cell populations that are important for maintaining local tissue integrity; dysregulation of these cells can lead to inflammatory diseases such as psoriasis and atopic dermatitis. Understanding how skin-resident immune cells are regulated is important in the effort to treat skin diseases. The majority of skin-homing and skin-resident lymphocytes express the chemokine receptor CCR10. Our lab has found that CCR10 is important for the homeostatic establishment of skin-resident lymphocytes. The skin-specific ligand of CCR10 is CCL27, a chemokine primarily expressed by keratinocytes. While the regulation and functions of CCL27 are not well understood we have found evidence to suggest that CCL27 has a homeostatic role in the skin. We report that CCL27 expression in keratinocytes and within regions of cycling hair follicles is developmentally regulated, independent of commensal bacterial stimulation. Further, CCL27 expression correlates with the localization of CCR10+ lymphocytes to specific regions within the skin. Newly generated CCL27-knockout mice show that the loss of CCL27 results in the diminished migration and localization of CCR10+ lymphocytes into the skin, particularly within regulatory and CD8+ T cell populations. Preliminary data also indicates CCL27-knockout mice had more severe skin inflammation than wild-type mice in a model of psoriasis. These findings reveal that the regulation of CCL27 expression is important for directing the localization of CCR10+ lymphocytes to specific niches of the skin, helping to maintain local homeostasis under steady-state conditions and hair follicle cycling, and that the loss of CCL27 may contribute to inflammatory diseases.