W129 - Investigating the Role of the Chemokine Receptor, CCR1 in Cutaneous Lupus Erythematosus Pathogenesis

Abstract Text: Investigating the role of the chemokine receptor, CCR1 in Cutaneous Lupus Erythematosus Pathogenesis
Mridushi Daga, Saeed Shakiba, Jillian Richmond

Introduction: Cutaneous Lupus Erythematosus (CLE) is an autoimmune disease that affects the skin, causing chronic inflammation. This inflammation leads to symptoms such as scaly rashes and lesions. Central to CLE pathogenesis is infiltration of leukocytes and proinflammatory chemokine production in the epidermis. These processes are regulated by various chemokine receptor axes. Studying these axes may help identify new targets for understanding and treating CLE.

Results: Using spatial transcriptomics, we analyzed 17 chemokine receptors in human skin biopsies from CLE patients and identified CCR1 as the most significantly upregulated compared to healthy samples. Olink proteomics of interstitial skin fluid from suction blister biopsies further confirmed this, revealing increased levels of multiple CCR1 ligands (CCL3, CCL7, CCL8, CCL23) in lesional blister fluid compared to healthy controls. In a novel adoptive T cell transfer CLE mouse model, CCR1 knockout in T cells conferred partial protection against the development of severe disease. Additionally, monocytes, which are among the first cells to infiltrate the skin, also express CCR1. We plan to test the CCR1 antagonist BX471 in our mouse model, as it blocks both T cells and monocytes, potentially offering better protection against disease.

Conclusions: The CCR1 chemokine axis plays a major role in recruiting disease-causing immune cells to the skin. Blocking this axis with antagonists may help protect against the development of CLE in our mouse model.