Many immune and non-immune cell types are known to produce TGF-β; however, the role of T regulatory (Treg) cell-intrinsic TGF-β is not clear. The results from a collaborative project with Prof. Talal Chatila’s lab at Children’s hospital, Boston, demonstrate that TGF-β1, the major TGF-β form produced by T cells, is important in maintaining immunological tolerance.
In a mouse model of food allergy that has a gain-of-function mutation in the interleukin-4Rα (IL-4Rα) chain gene (Il4raF709), Treg cells have decreased access at the Tgfb1 locus which was reversed by deletion of Stat6. These results are indicative of decreased expression of TGF-β in Treg cells in food allergy. A direct role of decreased TGF-β expression in Treg cells in promoting food allergy was supported by experiments involving overexpression of Tgfb1 transgene in Treg cells of Il4raF709 mice.
Furthermore, additional experiments demonstrated that Treg cell-specific monoallelic deletion of Tgfb1 locus promotes allergic response while biallelic Tgfb1 deletion precipitates autoimmunity. These results highlight dose dependent role of Treg cell-derived TGF-β in regulating allergy and autoimmunity.
Genome browser view demonstrating ATAC-seq profile of the Tgfb1 locus in Treg cells of the respective mouse strains (adapted from Immunity, 53(6):1202-1214.e6).
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