Loss of RPA1 Impairs Peripheral T Cell Homeostasis and Exacerbates Inflammatory Damage through Triggering T Cell Necroptosis.

ABSTRACT: The peripheral T cell pool is maintained at dynamic homeostasis through fine-tuning of thymic output and self-renewal of naïve T cells. Lymphopenia or reduced lymphocyte number is implicated in autoimmune diseases, yet little is known about the homeostatic mechanisms. Here, it is reported that the replication protein A1 (RPA1) plays a critical role in T cell homeostasis. Utilizing T cell-specific Rpa1-deficient (Rpa1^fl/fl Cd4-cre) mice, loss of Rpa1 results in lymphopenia through restraining peripheral T cell population and limiting TCR repertoire diversity. Moreover, Rpa1^fl/fl Cd4-cre mice exhibit increased susceptibility to inflammatory diseases, including colitis and hepatitis. Clinical analysis reveals that the expression of RPA1 is reduced in patients with ulcera

SUBMITTER: Song J 

PROVIDER: S-EPMC10104672 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature