| First Author | Wu T | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 10 | Pages | 4989-5000 |
| PubMed ID | 23045614 | Mgi Jnum | J:190588 |
| Mgi Id | MGI:5449275 | Doi | 10.4049/jimmunol.1200068 |
| Citation | Wu T, et al. (2012) Smad3-deficient CD11b(+)Gr1(+) myeloid-derived suppressor cells prevent allograft rejection via the nitric oxide pathway. J Immunol 189(10):4989-5000 |
| abstractText | Immunosuppressive CD11b(+)Gr1(+) myeloid-derived suppressor cells and TGF-beta have been shown to negatively regulate host immunity against allografts. Our results demonstrated that Smad3-deficient mice or mice reconstituted with Smad3-deficient hematopoietic cells rejected allogeneic skin or heart grafts in a significantly slower manner compared with littermates or wild-type (WT) control mice. Transplanted Smad3(-/-) recipients produced markedly less anti-donor IgG Abs, especially IgG1 and IgG2b subclasses. T cells in alloskin-grafted Smad3-deficient mice were more likely to participate in a Th2-type immune response, as evidenced by more Th2-specific transcription factor, GATA3 expression, and increased IL-4 and IL-10 production, as well as less Th1-specific transcription factor, T-bet expression, and decreased IL-2 and IFN-gamma production. More CD11b(+)Gr1(+) neutrophil infiltration and less monocyte/macrophage and T cell infiltration in allografts were observed in Smad3(-/-) recipients compared with WT recipients. Increased CXCL1 and CXCL2 as well as decreased CCL3, MCP-1, and RANTES chemokines in allografts of Smad3(-/-) recipients were consistently detected by real-time PCR. Further studies indicated that the increased CD11b(+)Gr1(+) myeloid cells in Smad3-deficient mice were immunosuppressive and responsible for the delayed allograft rejection mainly via an NO-dependent pathway. Thus, this study identifies Smad3 as an intrinsic negative regulator that critically inhibits the differentiation and function of immunosuppressive CD11b(+)Gr1(+) myeloid-derived suppressor cells. |
