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. 2018 Feb;28(2):253-256.
doi: 10.1038/cr.2018.7. Epub 2018 Jan 5.

m6A mRNA methylation sustains Treg suppressive functions

Jiyu Tong  1   2 , Guangchao Cao  2   3 , Ting Zhang  1 , Esen Sefik  2 , Maria Carolina Amezcua Vesely  2 , James P Broughton  4 , Shu Zhu  5 , Huabin Li  6 , Bin Li  1 , Lei Chen  1 , Howard Y Chang  4 , Bing Su  1   2 , Richard A Flavell  2   7 , Hua-Bing Li  1   2
Affiliations

m6A mRNA methylation sustains Treg suppressive functions

Jiyu Tong et al. Cell Res. 2018 Feb.
No abstract available

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Figures

Figure 1
Figure 1
Specific deletion of Mettl3 in Tregs led to loss of Treg suppression function and severe autoimmune diseases. (A) 7-week-old Mettl3f/f; Foxp3Cre mice developed severe autoimmune disease, lost hair, and had enlarged periphery lymph nodes (pLN). (B) Th1 and Th17 cytokine analysis by FACS of the spleen and periphery lymph nodes from Mettl3f/f; Foxp3Cre and WT control mice. (C) FACS analysis of Treg population (Foxp3+CD25+) at different days after birth, and the statistics is shown below (n = 7). (D) In vivo suppression assay by co-transferring naïve T cells only, naïve T cells with WT or Mettl3−/− Tregs into TCRβ−/− mice (n = 4). (E) In vitro suppression assay by co-culturing the WT naïve T cells with either KO Tregs or WT Treg cells at different ratios. The mixing ratio is shown above the graph, and the percentage of divided cells and statistics are shown on the right graph (n = 3). (F) RNA-Seq analysis of WT and Mettl3 KO Tregs isolated from spleen of one-week-old and four-week-old mice, and the Socs genes are among the most up-regulated genes. (G) m6A irCLIP-Seq analysis of CD4+ T cells shows m6A enrichment at 3′ UTR and 5′ UTR regions and confirms Socs genes are m6A targets (n = 2). (H) Phospho-kinase array with lysates of FACS-sorted WT or Mettl3−/− Tregs from 4-week-old mice; pSTAT5 signals decrease in the Mettl3 KO Tregs and are highlighted. (I) Signaling assay of the IL-2-STAT5 pathway with FACS-sorted pure WT and Mettl3 KO Tregs from 6-week-old mice (n = 3). *P < 0.05, **P < 0.01, ***P < 0.001.
See this image and copyright information in PMC

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