W109 - Dermatomyositis Skin Inflammation Is Associated with Type-i IFN Response and the Presence of pd1-high, CXCR5-, CXCL13+ CD4+ T Cells, Which Expands in Response to UVB Irradiation

Yuqing Wang; nazgol Sadat Haddadi; Shany ShermanBergman; Jillian Richmond; Ruth Ann Vleugels; Manuel Garber; Mehdi Rashighi

Abstract Text: Dermatomyositis (DM) is a rare inflammatory skin disease associated with chronic pruritic rash and UVB photosensitivity. Using single-cell RNA sequencing and flow cytometry, we identified a distinct population of CXCR5-, PD1-high, CXCL13+ CD4+ T helper cells only in lesional skin, which exhibited a type I interferon (IFN-I) signature, relatively stronger compared to other subsets of T cells.

Immunohistochemical analysis of lesional DM skin demonstrated that CXCL13 CD4 T cells tightly infiltrated around capillaries and small blood vessels in the dermis, but surprisingly no evidence of B or plasma cells aggregate.

Using ELISA on interstitial skin fluid captured via suction blistering, we discovered a significant elevation of both IFN-β and CXCL13 in lesional DM compared to non-lesional DM and healthy skin. Spatial transcriptomics of lesional skin revealed that T cells near basal keratinocytes (KCs) exhibited a stronger IFN-I signature.

Primary KCs obtained and cultured from DM skin exhibited an increased expression of IFN-I following exposure to UVB compared to healthy KCs, in vitro (p < 0.01). Further, we found that IFN-β induced a significantly higher expression of CXCL13 in CD4+ T cells isolated from the blood of DM patients compared to healthy, in vitro (p < 0.001). Moreover, UVB photoprovocation of clinically normal-appearing skin in a DM patient resulted in the expansion of CXCL13-producing T cells in vivo.

Taken together, our findings suggest that a pathologically enhanced IFN-I response following UVB exposure in DM KCs could lead to the expansion of CXCL13-producing CD4 T cells in the dermis and lead to skin inflammation.