N6‐ Methyladenosine defines a new checkpoint in γδ T cell development

Abstract T cells, which are derived from hematopoietic stem cells (HSCs), are the most important components of adaptive immune system. Based on the expression of αβ and γδ receptors, T cells are mainly divided into αβ and γδ T cells. In the thymus, they share common progenitor cells, while undergoing a series of well‐characterized and different developmental processes. N 6 ‐Methyladenosine (m 6 A), one of the most abundant modifications in mRNAs, plays critical roles in cell development and maintenance of function. Recently, we have demonstrated that the depletion of m 6 A demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells through the regulation of Jag1/Notch2 signaling, but not αβ T cells, indicating a checkpoint role of ALKBH5 and m 6 A modification in the early development of γδ T cells. Based on previous studies, many key pathway molecules, which exert dominant roles in γδ T cell fate determination, have been identified as the targets regulated by m 6 A modification. In this review, we mainly summarize the potential regulation between m 6 A modification and these key signaling molecules in the γδ T cell lineage commitment, to provide new perspectives in the checkpoint of γδ T cell development.