TGF-β in T regulatory cells

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 (Il4ra^F709), 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 Il4ra^F709 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.