Article ; Online: Resistance to Streptozotocin-Induced Autoimmune Diabetes in Absence of Complement C3: Myeloid-Derived Suppressor Cells Play a Role.
PloS one
2013 Volume 8, Issue 6, Page(s) e66334
Abstract: ... cells (MDSC), which act as regulators in autoimmunity, play a role in resistance to diabetes in absence ... These findings indicate that MDSC are implicated in resistance to STZ-induced diabetes in the absence ... The contribution of complement to the development of autoimmune diabetes has been proposed recently ...
| Abstract | 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-β (TGF-β) are crucial for MDSC induction in STZ-treated C3-/- mice as depletion of Tregs or blocking TGF-β 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. |
|---|---|
| MeSH term(s) | Animals ; Coculture Techniques ; Complement C3/immunology ; Cytokines/immunology ; Diabetes Mellitus, Type 1/immunology ; Down-Regulation ; Inflammation Mediators/immunology ; Islets of Langerhans/immunology ; Islets of Langerhans/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Myeloid-Derived Suppressor Cells/immunology ; Streptozocin |
| Chemical Substances | Complement C3 ; Cytokines ; Inflammation Mediators ; Streptozocin (5W494URQ81) |
| Language | English |
| Publishing date | 2013-06-18 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 1932-6203 |
| ISSN (online) | 1932-6203 |
| DOI | 10.1371/journal.pone.0066334 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.
Inter-library loan at ZB MED
Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.