IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus Journal Article
| Authors: | Hemmers, S.; Schizas, M.; Azizi, E.; Dikiy, S.; Zhong, Y.; Feng, Y.; Altan-Bonnet, G.; Rudensky, A. Y. |
| Article Title: | IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus |
| Abstract: | Regulatory T (T reg) cells, a specialized subset of CD4+ T cells, are essential to prevent fatal autoimmunity. Expression of the T reg lineage-defining transcription factor Foxp3, and therefore their differentiation in the thymus, is dependent upon T cell receptor (TCR) and interleukin-2 (IL-2) signaling. Here, we report that the majority of IL-2-producing cells in the thymus are mature CD4 single-positive (CD4SP) thymocytes and that continuous IL-2 production sustained thymic T reg cell generation and control of systemic immune activation. Furthermore, single-cell RNA sequencing analysis of CD4 thymocyte subsets revealed that IL-2 was expressed in self-reactive CD4SP thymocytes, which also contain T reg precursor cells. Thus, our results suggest that the thymic T reg cell pool size is scaled by a key niche factor, IL-2, produced by self-reactive CD4SP thymocytes. This IL-2-dependent scaling of thymic T reg cell generation by overall self-reactivity of a mature post-selection thymic precursor pool may likely ensure adequate control of autoimmunity. © 2019 Hemmers et al. |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 216 |
| Issue: | 11 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2019-11-01 |
| Start Page: | 2466 |
| End Page: | 2478 |
| Language: | English |
| DOI: | 10.1084/jem.20190993 |
| PUBMED: | 31434685 |
| PROVIDER: | scopus |
| PMCID: | PMC6829602 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 December 2019 -- Source: Scopus |
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