Full thickness tail skin from alloreactive C3+/+ B6 and C3?/? B6 mice was transplanted into MHC-II molecule disparate Bm12 recipients, and syngeneic Bm12 used as a negative control. allograft survival, which is further confirmed to be associated with increased CD4+ CD25+ Treg cell population expansion and attenuated Th1/Th17 response. The complement system is one of the major contributors to innate immunity and contains a series of soluble and cell surface proteins, including plasma components, specific receptors and diverse regulators. It serves as the first line of defense against invading pathogens by applying complement activation elements acting with antibodies, phagocytes or through the formation of the membrane attack complex (MAC)1,2. In addition to its vital role in innate immunity, increasing evidence has indicated that the complement system regulates adaptive immunity, especially the antigen-specific T cell response3,4. Furthermore, the complement system plays a critical role in transplantation success, Dihydroactinidiolide and has been shown to participate in the pathogenesis of ischemia-reperfusion injury, to promote alloantibody-mediated rejection, to modulate the alloreactive T cell response and to contribute to progressive chronic allograft rejection5,6,7. Three pathways of complement activation: the classic pathway, lectin pathway, and alternative pathway, which of them converge at the level of complement component 3 (C3) convertase, from which functional products are generated in a sequential manner5. Studies have demonstrated that C3 plays a critical role in the regulation of T cell responses to autoimmune disease, viral infection and transplant rejection8,9,10,11,12. As compared with systemic C3 produced in the liver, local C3 is mainly generated by diverse tissue-resident cells (such as tubular cells in the kidney, endothelial and epithelial cells), antigen presentation cells (APCs) and T cells13,14,15,16,17. The role of C3 in allograft rejection remains controversial. It was indicated that Dihydroactinidiolide intra-renal C3 deficiency (C3?/?) prolonged renal allograft survival and caused a defective alloreactive T cell response when compared with C3 positive (C3+/+) allografts18. On the contrary, in a minor H disparate skin transplant model, results suggested that C1q or C3 deficiency (C1q?/? or C3?/?) accelerated graft rejection as well as impaired intranasal tolerance induction19. Several studies have revealed that C3 deficiency is associated with attenuated Th1/Th17 responses14,20,21. CD4+ CD25+ Foxp3+ regulatory T (Treg) cells are thought to be critical for promoting peripheral tolerance, limiting chronic inflammatory disease and relieving autoimmune disease22,23,24. Strikingly, the absence of C3aR and Rabbit polyclonal to UBE2V2 C5aR signalling in CD4+ T cells has recently been confirmed to favour Treg expansion and survival25,26. Nevertheless, it remains unclear how C3 affects Treg cells development and regulates the balance between Treg cells and Th1/Th17 cells response during transplantation rejection. In this study, we investigated the role of C3 in a single MHC-II molecule mismatched murine model of allograft rejection. We demonstrate that graft C3 deficiency can clearly prolong skin allograft survival, partly by expanding the population of CD4+ CD25+ Treg cells and attenuating Th1/Th17 cell responses in recipients with C3?/? allografts. Results Increased survival of C3?/? allografts in an MHC-II molecule Dihydroactinidiolide disparate skin transplant model To explore the exact role of C3 in allograft rejection, we established an MHC-II molecule disparate skin transplant model. Full thickness tail skin from alloreactive C3+/+ B6 and C3?/? B6 mice was transplanted into MHC-II molecule disparate Bm12 recipients, and syngeneic Bm12 utilized as a poor control. Weighed against C3+/+ allografts, that have been turned down within 17 times after transplantation totally, 60% of C3?/? allografts survived until time 30 (Fig. 1a, p? ?0.0001). These total results indicate that C3 deficiency could prolong MHC-II disparate epidermis allograft survival. It had been reported which the T cells in C3 previously?/? mice haven’t any intrinsic defect27,28. In keeping with these outcomes by Carroll recommended that regional intra-renal supplement C3 production pursuing donor brain loss of life is closely connected with renal graft function early after transplantation35. In keeping with.