Ikaros is a principal regulator of Aire⁺ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance.

ABSTRACT: Mutations in the gene encoding the zinc-finger transcription factor Ikaros (IKZF1) are found in patients with immunodeficiency, leukemia, and autoimmunity. Although Ikaros has a well-established function in modulating gene expression programs important for hematopoietic development, its role in other cell types is less well defined. Here, we uncover functions for Ikaros in thymic epithelial lineage development in mice and show that Ikzf1 expression in medullary thymic epithelial cells (mTECs) is required for both autoimmune regulator-positive (Aire⁺) mTEC development and tissue-specific antigen (TSA) gene expression. Accordingly, TEC-specific deletion of Ikzf1 in mice results in a profound decrease in Aire⁺ mTECs, a global loss of TSA gene express

SUBMITTER: Sin JH 

PROVIDER: S-EPMC11433069 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature