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

T cells, which are derived from hematopoietic stem cells (HSCs), are the most important components of adaptive immune system. Based on the expression of alpha beta and gamma delta receptors, T cells are mainly divided into alpha beta and gamma delta 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.d T cells through the regulation of Jag1/Notch2 signaling, but not alpha beta T cells, indicating a checkpoint role of ALKBH5 and m(6)A modification in the early development of gamma delta T cells. Based on previous studies, many key pathway molecules, which exert dominant roles in gamma delta 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 gamma delta T cell lineage commitment, to provide new perspectives in the checkpoint of gamma delta T cell development.

Automated summary

T cells derived from hematopoietic stem cells are divided into alpha beta and gamma delta T cells and undergo different developmental processes. The depletion of m(6)A demethylase ALKBH5 specifically leads to an expansion of gamma delta T cells through signaling regulation. This indicates the important role of ALKBH5 and m(6)A modification in the early development of gamma delta T cells.