| First Author | Kanamori M | Year | 2018 |
| Journal | Int Immunol | Volume | 30 |
| Issue | 8 | Pages | 357-373 |
| PubMed ID | 29982622 | Mgi Jnum | J:264043 |
| Mgi Id | MGI:6192401 | Doi | 10.1093/intimm/dxy043 |
| Citation | Kanamori M, et al. (2018) Reprogramming of Th1 cells into regulatory T cells through rewiring of the metabolic status. Int Immunol 30(8):357-373 |
| abstractText | T helper type 1 (Th1) cells form one of the most stable CD4 T-cell subsets, and direct conversion of fully differentiated Th1 to regulatory T (Treg) cells has been poorly investigated. Here, we established a culture method for inducing Foxp3 from Th1 cells of mice and humans. This is achieved simply by resting Th1 cells without T-cell receptor ligation before stimulation in the presence of transforming growth factor-beta (TGF-beta). We named the resulting Th1-derived Foxp3+ cells Th1reg cells. Mouse Th1reg cells showed an inducible Treg-like phenotype and suppressive ability both in vitro and in vivo. Th1reg cells could also be induced from in vivo-developed mouse Th1 cells. Unexpectedly, the resting process enabled Foxp3 expression not through epigenetic changes at the locus, but through metabolic change resulting from reduced mammalian target of rapamycin complex 1 (mTORC1) activity. mTORC1 suppressed TGF-beta-induced phosphorylation of Smad2/3 in Th1 cells, which was restored in rested cells. Our study warrants future research aiming at development of immunotherapy with Th1reg cells. |
