| First Author | van der Touw W | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 12 | Pages | 5921-5 |
| PubMed ID | 23690475 | Mgi Jnum | J:204834 |
| Mgi Id | MGI:5543539 | Doi | 10.4049/jimmunol.1300847 |
| Citation | van der Touw W, et al. (2013) Cutting edge: Receptors for C3a and C5a modulate stability of alloantigen-reactive induced regulatory T cells. J Immunol 190(12):5921-5 |
| abstractText | CD4(+)Foxp3(+) regulatory T cells (Treg) are critical regulators of immune homeostasis and self-tolerance. Whereas thymic-derived or natural Treg stably express Foxp3, adaptive or induced Treg (iTreg) generated from peripheral CD4 T cells are susceptible to inflammation-induced reversion to pathogenic effector T cells. Building upon our previous observations that T cell-expressed receptors for C3a (C3aR) and C5a (C5aR) drive Th1 maturation, we tested the impact of C3aR/C5aR signaling on induction and stability of alloreactive iTreg. We observed that genetic deficiency or pharmacological blockade of C3aR/C5aR signaling augments murine and human iTreg generation, stabilizes Foxp3 expression, resists iTreg conversion to IFN-gamma/TNF-alpha-producing efffector T cells, and, as a consequence, limits the clinical expression of graft-versus-host disease. Taken together, the findings highlight the expansive role of complement as a crucial modulator of T cell alloimmunity and demonstrate proof-of-concept that targeting C3a/C3aR and C5a/C5aR interactions could facilitate iTreg-mediated tolerance to alloantigens in humans. |
