Cbf-β is required for development and differentiation of murine mucosal-associated invariant T cells

Abstract

Abstract Mucosal-associated invariant T (MAIT) cells primarily reside in mucosal tissues and tissues exposed to the environment to act as a defense against microbial threats. Additionally, they are also involved in a broad spectrum of diseases, including infection, cancer, allergy, and autoimmunity. Although some transcriptional factors and micro-RNA have been recently identified to regulate MAIT cell development and differentiation, a significant gap in our knowledge of MAIT cell regulation still exists. The core binding factor subunit beta (Cbf-β) is a non-DNA binding protein forming a heterodimer with RUNX family proteins to regulate diverse signaling pathways which maintain homeostasis of a wide range of immune cells. To understand the role of Cbf-β in MAIT cell development and function, we generated T cell lineage specific Cbf-β knockout mice (CD4cre+Cbf-β KO) and inducible Cbf-β knockdown mice (UBCcre+Cbf-β KO). We found that Cbf-β deficiency impaired thymic MAIT cell development and interrupted MAIT1 and MAIT17 differentiation. Additionally, inducible knockdown of Cbf-β reduced activation and cytotoxicity in peripheral MAIT cells. Our work suggests that Cbf-β is required for thymic MAIT cell development and MAIT1 and MAIT17 commitment in addition to playing a role in MAIT cell activation and cytotoxicity. Overall, Cbf-β may serve as a novel target to modulate MAIT cells in MAIT cell-based immunotherapies. This study was supported by Henry Ford Immunology Program grants (T71016 and T71017) to QSM and LZ, by the National Institutes of Health (NIH) grants R61AR076803, R01AR063611, and R01AR069681 to QSM, RO1AR072046 to LZ.