| First Author | Gao X | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 6 | Pages | e66334 |
| PubMed ID | 23824734 | Mgi Jnum | J:203459 |
| Mgi Id | MGI:5527048 | Doi | 10.1371/journal.pone.0066334 |
| Citation | Gao X, et al. (2013) Resistance to Streptozotocin-Induced Autoimmune Diabetes in Absence of Complement C3: Myeloid-Derived Suppressor Cells Play a Role. PLoS One 8(6):e66334 |
| abstractText | The contribution of complement to the development of autoimmune diabetes has been proposed recently. The underlying mechanisms, however, remain poorly understood. We hypothesize that myeloid-derived suppressor cells (MDSC), which act as regulators in autoimmunity, play a role in resistance to diabetes in absence of complement C3. Indeed, MDSC number was increased significantly in STZ-treated C3-/- mice. These cells highly expressed arginase I and inducible nitric oxide synthase (iNOS). Importantly, depletion of MDSC led to the occurrence of overt diabetes in C3-/- mice after STZ. Furthermore, C3-/- MDSC actively suppressed diabetogenic T cell proliferation and prevented/delayed the development of diabetes in arginase and/or iNOS-dependent manner. Both Tregs and transforming growth factor-beta (TGF-beta) are crucial for MDSC induction in STZ-treated C3-/- mice as depletion of Tregs or blocking TGF-beta bioactivity dramatically decreased MDSC number. These findings indicate that MDSC are implicated in resistance to STZ-induced diabetes in the absence of complement C3, which may be helpful for understanding of mechanisms underlying preventive effects of complement deficiency on autoimmune diseases. |
