IKK2 controls the inflammatory potential of tissue-resident regulatory T cells in a murine gain of function model.

ABSTRACT: Loss-of-function mutations have provided crucial insights into the immunoregulatory actions of Foxp3+ regulatory T cells (Tregs). By contrast, we know very little about the consequences of defects that amplify aspects of Treg function or differentiation. Here we show that mice heterozygous for an Ikbkb gain-of-function mutation develop psoriasis. Doubling the gene dose (Ikbkb^GoF/GoF) results in dactylitis, spondylitis, and characteristic nail changes, which are features of psoriatic arthritis. Ikbkb^GoF mice exhibit a selective expansion of Foxp3 + CD25+ Tregs of which a subset express IL-17. These modified Tregs are enriched in both inflamed tissues, blood and spleen, and their transfer is sufficient to induce disease without conventional T cells. Single-cell transcri

SUBMITTER: Cardinez C 

PROVIDER: S-EPMC10963799 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature