| First Author | Li Y | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 10 | Pages | 2910-2922 |
| PubMed ID | 30291167 | Mgi Jnum | J:267008 |
| Mgi Id | MGI:6257973 | Doi | 10.4049/jimmunol.1700638 |
| Citation | Li Y, et al. (2018) Helminth-Induced Production of TGF-beta and Suppression of Graft-versus-Host Disease Is Dependent on IL-4 Production by Host Cells. J Immunol 201(10):2910-2922 |
| abstractText | Helminths stimulate the secretion of Th2 cytokines, like IL-4, and suppress lethal graft-versus-host disease (GVHD) after bone marrow transplantation. This suppression depends on the production of immune-modulatory TGF-beta and is associated with TGF-beta-dependent in vivo expansion of Foxp3(+) regulatory T cells (Treg). In vivo expansion of Tregs is under investigation for its potential as a therapy for GVHD. Nonetheless, the mechanism of induced and TGF-beta-dependent in vivo expansion of Tregs, in a Th2 polarized environment after helminth infection, is unknown. In this study, we show that helminth-induced IL-4 production by host cells is critical to the induction and maintenance of TGF-beta secretion, TGF-beta-dependent expansion of Foxp3(+) Tregs, and the suppression of GVHD. In mice with GVHD, the expanding donor Tregs express the Th2-driving transcription factor, GATA3, which is required for helminth-induced production of IL-4 and TGF-beta. In contrast, TGF-beta is not necessary for GATA3 expression by Foxp3(+) Tregs or by Foxp3(-) CD4 T cells. Various cell types of innate or adaptive immune compartments produce high quantities of IL-4 after helminth infection. As a result, IL-4-mediated suppression of GVHD does not require invariant NKT cells of the host, a cell type known to produce IL-4 and suppress GVHD in other models. Thus, TGF-beta generation, in a manner dependent on IL-4 secretion by host cells and GATA3 expression, constitutes a critical effector arm of helminthic immune modulation that promotes the in vivo expansion of Tregs and suppresses GVHD. |
