Tu113 - Characterizing Skin Resident and Recirculating Memory T-cells in Human and Murine Cutaneous Lupus Erythematosus

Ummugulsum Yildiz-Altay – Post Doctoral Associate, Department of Dermatology, University of Massachusetts Chan Medical School; Nazgol-Sadat Haddadi – Post Doctoral Associate, Department of Dermatology, University of Massachusetts Chan Medical School; Khashayar Afshari – Post Doctoral Associate, Department of Dermatology, University of Massachusetts Chan Medical School; Karen Dresser – Research Lab Supervisor, Anatomic Pathology, University of Massachusetts Chan Medical School; Mehdi Rashighi – Assistant Professor, Department of Dermatology, University of Massachusetts Chan Medical School; Ann Marshak-Rothstein – Professor, Department of Rheumatology, University of Massachusetts Chan Medical School; April Deng – Pathologist, Department of Anatomic Pathology, University of Massachusetts Chan Medical School; Jillian Richmond – Assistant Professor, Department of Dermatology, University of Massachusetts Chan Medical School

Abstract Text: Cutaneous lupus erythematosus (CLE) is a severe autoimmune skin disease. Autoreactive T cells differentiate into skin resident memory T cells (TRM) in CLE lesions and persist even when patients are in remission. We postulate that targeting molecules necessary for autoreactive T cells' residency and function will serve as a novel therapeutic approach to effectively prevent flare-ups. To study TRM in CLE, we used a mouse model and human blister biopsies to analyze T cell characteristics using flow cytometry. Most skin TRM expressed CD69 (70%) in CLE mice. However, many of these cells were capable of recirculating (TRCM) based on their expression of CD62L. In human blister biopsies, we found that skin CD8+ T cells were CD69+CD103+, but not CD4+ T cells, which tended to express CD122 instead. As expected, many blood T cells are negative for these markers. We noted high variability in CD122/CD103 expression; therefore, we analyzed patient samples based on clinical subtype, specifically whether or not they experienced cutaneous (SCLE) or systemic lupus (SLE). We found that SCLE patients had CD122+ CD4 T cells in lesional/nonlesional skin, whereas their CD8 skin T cells expressed primarily CD103. Strikingly, CD4/CD8 T cells in the blood of patients who also experienced SLE had CD122, which was very low in SCLE patients. Examination of spatial transcriptomic data from CLE skin biopsies confirmed the expression of TRM and TRCM markers in CD3+ regions of interest. Together, these data suggest that the ability of TRM to recirculate may predispose systemic involvement in CLE patients.