Mast Cells Regulate CD4+ T Cell Differentiation in Absence of Antigen Presentation

Abstract

Given their unique capacity for antigen uptake, processing, and presentation, antigen presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. Using bone marrow-derived mast cells and mast cell (MC) deficient mice, our in vivo and in vitro findings indicate that following NAD+ administration MCs, exclusively, promote CD4+ T-cell differentiation, both in absence of antigen and independently of major APCs. Moreover, we found that MCs mediated CD4+ T-cell differentiation independently of MHC-II and TCR signaling machinery. Although treatment with NAD+ resulted in a decreased MHC-II expression on CD11c+ cells, MC-mediated CD4+ T-cell differentiation rendered mice resistant to lethal doses of Listeria monocytogenes. Collectively, our study unravels a novel cellular and molecular pathway that regulates innate and adaptive immunity via MCs and may pave the way for novel therapeutic approaches in the context of immunodeficiencies and antimicrobial resistance.