CXCL9, CXCL10, and CCL19 synergistically recruit T-lymphocytes to skin in lichen planus.

Abstract

Lichen planus (LP) is a chronic, debilitating, inflammatory disease of the skin and mucous membranes that affects 1% to 2% of Americans. Its molecular pathogenesis remains poorly understood, and there are no FDA-approved treatments. We performed single cell RNA sequencing on paired blood and skin samples (lesional and non-lesional tissue) from 7 LP patients. We discovered that LP keratinocytes and fibroblasts specifically secrete a combination of CXCL9, CXCL10, and CCL19 cytokines. Using an in vitro migration assay with primary human T cells, we demonstrated that CCL19 in combination with either cytokine synergistically enhanced recruitment of CD8 T cells, more than the sum of individual cytokines. Moreover, exhausted T cells in lesional LP skin secreted CXCL13, which along with CCL19 also enhanced recruitment of T cells, suggesting a feed-forward loop in LP. Finally, LP blood revealed decreased circulating naïve CD8 T cells compared to healthy volunteers, consistent with recruitment to skin. Molecular analysis of LP skin and blood samples increased our understanding of disease pathogenesis and identified CCL19 as a new therapeutic target for treatment.