Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation.

ABSTRACT: Peripherally derived regulatory T cells (pTregs) have a prominent role in maintaining intestinal immune homeostasis. In cases of phosphoinositide-3-kinase δ (PI3Kδ) inactivation, such as in patients receiving PI3Kδ inhibitor idelalisib as a cancer treatment, breakdown of intestinal immune tolerance occurs frequently in the form of diarrhea and colon inflammation. In a mouse model of systemic PI3Kδ inactivation, both enhancement of antitumor immunity and colitis have been described as a result of Treg impairment. However, in view of the critical role for Tregs in the prevention of systemic autoimmunity, the basis for such tissue-restricted breach of immune tolerance upon loss of PI3Kδ function is not yet understood. We report here that mice lacking PI3Kδ activity do not suffer a general def

SUBMITTER: Lim EL 

PROVIDER: S-EPMC12501401 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature