A novel function of CCL27 in the localization of skin-homing CCR10+ lymphocytes

Abstract

Abstract The skin contains an abundance of resident lymphocytes that play vital roles in the first line of defense. Dysregulation of the skin immune system could lead to diseases such as psoriasis and atopic dermatitis; studying the immune cells that contribute to skin immune homeostasis is crucial to understanding these diseases. Our lab has found that various subsets of skin-homing lymphocytes that express the chemokine receptor CCR10 have homeostatic functions. The skin specific ligand to CCR10 is CCL27. We found that the expression pattern of CCL27 in the skin of mice is similar to humans: low expression at a young age with a gradual upregulation into adulthood. This upregulation of CCL27 does not require the stimulation of skin colonizing bacteria, as germ free mice did not significantly differ from specific pathogen free mice in their expression of CCL27, suggesting an intrinsic regulatory mechanism for CCL27 expression. CCR10-expressing cells were found to concentrate near the hair follicles, suggesting a role for CCL27/CCR10 in the localization of these cells to specific microstructures. Preliminary analysis of skin-draining lymph node sections from CCR10+/EGFP vs CCR10EGFP/EGFP mice show differential localization of lymphocytes around the vessel-rich medulla. Further, lymphatic endothelial cells from the skin draining lymph nodes express CCL27. These findings indicate a novel role of CCL27 in directing the migration and localization of CCR10+ cells within the skin-draining lymph nodes and skin.