associate student researcher California State Univ., San Marcos San Diego, California, United States
Disclosure(s):
Nashea Lampkins, MS: No financial relationships to disclose
Introduction/Rationale: Alopecia areata is an autoimmune skin disease characterized by nonscarring, patchy hair loss, and affects roughly 2% of the global population. The onset of alopecia areata involves both genetic and environmental factors, leading to the loss of immune privilege. Gamma Delta T cells help regulate skin homeostasis and are elevated during alopecia areata; however, their role in disease progression remains unclear.
Methods: By reanalyzing publicly available single-cell RNA sequencing data from mouse and human skin, we identified genes upregulated in gamma delta T cells during alopecia areata. In humans, Vδ1 T cells respond to stress in alopecia areata by upregulating heat shock response genes (HSP70, HSP90AA1, HSPA1A, HSPA1B, DNAJB1). We validated HSP70 upregulation by skin gamma delta T cells in the C3H/HeJ mouse model of alopecia areata using immunofluorescent microscopy.
Results: Further, murine skin gd T cells also up-regulate chaperones, including CD74 and receptors that regulate T cell activation, such as Ly6A/E, in alopecia areata. We quantified CD74 and Ly6A/E expression in the skin of mice with alopecia areata and found upregulation at the hair follicle, upper dermis, and epidermis. To identify which cells are regulating gd T cell stress and activation, we further examined single-cell RNA sequencing data and have identified the genes expressed by helper CD4+ T cells to regulate gd T cell stress and activation responses during alopecia areata.
Conclusion: Our findings show that T cells are undergoing a prominent stress response in response to alopecia areata, which leads to their activation, making them interesting targets for therapeutics.
