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CXCL9, CXCL10, and CCL19 synergistically recruit T lymphocytes to skin in lichen planus
Anna E. Kersh, … , Olivia Ahart, Thomas H. Leung
Anna E. Kersh, … , Olivia Ahart, Thomas H. Leung
Published August 27, 2024
Citation Information: JCI Insight. 2024;9(20):e179899. https://doi.org/10.1172/jci.insight.179899.
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Research Article Dermatology

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

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Abstract

Lichen planus (LP) is a chronic, debilitating, inflammatory disease of the skin and mucous membranes that affects 1%–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 nonlesional tissue) from 7 patients with LP. 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 of the other 2 cytokines synergistically enhanced recruitment of CD8+ T cells more than any individual cytokine. 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 naive CD8+ T cells compared with that in 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.

Authors

Anna E. Kersh, Satish Sati, Jianhe Huang, Christina Murphy, Olivia Ahart, Thomas H. Leung

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