| First Author | Kawamoto S | Year | 2004 |
| Journal | J Clin Invest | Volume | 114 |
| Issue | 3 | Pages | 399-407 |
| PubMed ID | 15286806 | Mgi Jnum | J:91728 |
| Mgi Id | MGI:3050275 | Doi | 10.1172/JCI19082 |
| Citation | Kawamoto S, et al. (2004) The anaphylatoxin C3a downregulates the Th2 response to epicutaneously introduced antigen. J Clin Invest 114(3):399-407 |
| abstractText | Mechanical injury to the skin results in activation of the complement component C3 and release of the anaphylatoxin C3a. C3a binds to a seven-transmembrane G protein-coupled receptor, C3aR. We used C3aR(-/-) mice to examine the role of C3a in a mouse model of allergic inflammation induced by epicutaneous sensitization with OVA. C3aR(-/-) mice exhibited an exaggerated Th2 response to epicutaneous but not to intraperitoneal sensitization with OVA, as evidenced by significantly elevated levels of serum OVA-specific IgG1 and significantly increased secretion of the Th2 cytokines IL-4, IL-5, and IL-10 by antigen-stimulated splenocytes. Presentation of OVA peptide by C3aR(-/-) APCs caused significantly more IL-4 and IL-5 secretion by T cells from OVA-T cell receptor (OVA-TCR) transgenic mice compared with presentation by WT APCs. C3a inhibited the ability of splenocytes, but not of highly purified T cells, to secrete Th2 cytokines in response to TCR ligation. This inhibition was mediated by IL-12 secreted by APCs in response to C3a. These results suggest that C3a-C3aR interactions inhibit the ability of APCs to drive Th2 cell differentiation in response to epicutaneously introduced antigen and may have important implications for allergic skin diseases. |
