| First Author | Strainic MG | Year | 2013 |
| Journal | Nat Immunol | Volume | 14 |
| Issue | 2 | Pages | 162-71 |
| PubMed ID | 23263555 | Mgi Jnum | J:192613 |
| Mgi Id | MGI:5465493 | Doi | 10.1038/ni.2499 |
| Citation | Strainic MG, et al. (2012) Absence of signaling into CD4(+) cells via C3aR and C5aR enables autoinductive TGF-beta1 signaling and induction of Foxp3(+) regulatory T cells. Nat Immunol 14(2):162-71 |
| abstractText | Signaling through the G protein-coupled receptors for the complement fragments C3a and C5a (C3aR and C5aR, respectively) by dendritic cells and CD4(+) cells provides costimulatory and survival signals to effector T cells. Here we found that when signals from C3aR and C5aR were not transduced into CD4(+) cells, signaling via the kinases PI(3)Kgamma, Akt and mTOR ceased, activation of the kinase PKA increased, autoinductive signaling by transforming growth factor-beta1 (TGF-beta1) initiated and CD4(+) T cells became Foxp3(+) induced regulatory T cells (iT(reg) cells). Endogenous TGF-beta1 suppressed signaling through C3aR and C5aR by preventing the production of C3a and C5a and upregulating C5L2, an alternative receptor for C5a. The absence of signaling via C3aR and C5aR resulted in lower expression of costimulatory molecules and interleukin 6 (IL-6) and more production of IL-10. The resulting iT(reg) cells exerted robust suppression, had enhanced stability and suppressed ongoing autoimmune disease. Antagonism of C3aR and C5aR can also induce functional human iT(reg) cells. |
