Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection.
A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the expansion of innate-like αβ T cells known as invariant natural killer T (iNKT) cells. However, it remains to be determined whether Id proteins differentially regulate these distinct lineage choices in early stages of T cell development. In this manuscript, we report that in Id-deficient mice, uninhibited activity of the E protein family member E2A mediates activation of genes that support iNKT cell development and function. There is also biased rearrangement in Id-deficient DP cells that promotes selection into the iNKT lineage in these mice. The observed expansion of iNKT cells is not abrogated by blocking pre-TCR signaling, which is required for conventional αβ T cell development. Finally, E2A is found to be a key transcriptional regulator of both iNKT and γδNKT lineages, which appear to have shared lineage history. Therefore, our study reveals a previously unappreciated role of E2A in coordinating the development of the iNKT lineage at an early stage, prior to their TCR-mediated selection alongside conventional αβ T cells.
['Roy|Sumedha|S|', 'Moore|Amanda J|AJ|', 'Love|Cassandra|C|', 'Reddy|Anupama|A|', 'Rajagopalan|Deepthi|D|', 'Dave|Sandeep S|SS|', 'Li|Leping|L|', 'Murre|Cornelis|C|', 'Zhuang|Yuan|Y|']
D000818:Animals D051792:Basic Helix-Loop-Helix Transcription Factors D002454:Cell Differentiation D051796:Inhibitor of Differentiation Proteins D018345:Mice, Knockout D055611:Natural Killer T-Cells D011948:Receptors, Antigen, T-Cell
Id proteins natural killer T cells E2A innate lymphocytes thymus