A22-13 Cxcr6 Expression and Function in Pulmonary Sarcoidosis

Pulmonary fibrosis is the leading contributor to morbidity and mortality in sarcoidosis; however, the therapeutic options remain elusive. CD4+ T cells have been reported to exhibit dysregulated phenotypes in sarcoidosis, but their contribution to disease progression remains unclear. To address this gap, we used a Propionibacterium acnes-induced sarcoid-like mouse model to investigate the role of CD4+ T cells. The results revealed an expansion of CXCR6+ CD4+ T cells during the phase of pulmonary fibrosis. These cells exhibited pro-inflammatory and pro-fibrotic profiles. Moreover, analysis of human sarcoidosis samples revealed that CXCR6+ CD4+ T cells were enriched within sarcoid lesions across various affected tissues, including the lungs, muscle, and skin. Finally, treatment with an anti-CXCR6 antibody significantly decreased the proportions of CD4+ Th1, Th17, and Th17.1 subsets, and, most importantly, alleviated pulmonary fibrosis. In conclusion, our data reveal CXCR6 as a promising and actionable therapeutic target for repressing fibrosis progression in sarcoidosis patients.