id proteins suppress e2a-driven invariant natural killer t cell development prior to tcr selection
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2018
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Abstract
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.
| Reference Key |
roy2018frontiersid
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|---|---|
| Authors | ;Sumedha Roy;Amanda J. Moore;Cassandra Love;Anupama Reddy;Deepthi Rajagopalan;Sandeep S. Dave;Leping Li;Cornelis Murre;Yuan Zhuang |
| Journal | sudebno-meditsinskaia ekspertiza |
| Year | 2018 |
| DOI |
10.3389/fimmu.2018.00042
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