| First Author | Ding C | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 33 | Pages | e2203318119 |
| PubMed ID | 35939687 | Mgi Jnum | J:340652 |
| Mgi Id | MGI:7437433 | Doi | 10.1073/pnas.2203318119 |
| Citation | Ding C, et al. (2022) RNA m(6)A demethylase ALKBH5 regulates the development of gammadelta T cells. Proc Natl Acad Sci U S A 119(33):e2203318119 |
| abstractText | gammadelta T cells are an abundant T cell population at the mucosa and are important in providing immune surveillance as well as maintaining tissue homeostasis. However, despite gammadelta T cells' origin in the thymus, detailed mechanisms regulating gammadelta T cell development remain poorly understood. N(6)-methyladenosine (m(6)A) represents one of the most common posttranscriptional modifications of messenger RNA (mRNA) in mammalian cells, but whether it plays a role in gammadelta T cell biology is still unclear. Here, we show that depletion of the m(6)A demethylase ALKBH5 in lymphocytes specifically induces an expansion of gammadelta T cells, which confers enhanced protection against gastrointestinal Salmonella typhimurium infection. Mechanistically, loss of ALKBH5 favors the development of gammadelta T cell precursors by increasing the abundance of m(6)A RNA modification in thymocytes, which further reduces the expression of several target genes including Notch signaling components Jagged1 and Notch2. As a result, impairment of Jagged1/Notch2 signaling contributes to enhanced proliferation and differentiation of gammadelta T cell precursors, leading to an expanded mature gammadelta T cell repertoire. Taken together, our results indicate a checkpoint role of ALKBH5 and m(6)A modification in the regulation of gammadelta T cell early development. |
