| First Author | Ding W | Year | 2022 |
| Journal | J Immunol | Volume | 208 |
| Issue | 3 | Pages | 633-641 |
| PubMed ID | 35031579 | Mgi Jnum | J:322306 |
| Mgi Id | MGI:7257932 | Doi | 10.4049/jimmunol.2100139 |
| Citation | Ding W, et al. (2022) Regulation of Cutaneous Immunity In Vivo by Calcitonin Gene-Related Peptide Signaling through Endothelial Cells. J Immunol 208(3):633-641 |
| abstractText | Calcitonin gene-related peptide (CGRP) can bias the outcome of Ag presentation to responsive T cells in vitro away from Th1-type immunity and toward the Th2 and Th17 poles through actions on endothelial cells (ECs). To test the in vivo significance of this observation, we engineered a mouse lacking functional CGRP receptors on ECs (EC receptor activity modifying protein 1 [RAMP1] knockout mice). On percutaneous immunization to 1-fluoro-2,4-dinitrobenzene, stimulated CD4(+) T cells from draining lymph nodes showed significantly reduced IL-17A expression with significantly increased IFN-gamma, IL-4, and IL-22 expression at the protein and mRNA levels compared with control mice. Retinoic acid receptor-related orphan receptor gamma t mRNA was significantly reduced, while mRNAs for T-box expressed in T cells and GATA binding protein 3 were significantly increased. In addition, EC RAMP1 knockout mice had significantly reduced contact hypersensitivity responses, and systemic administration of a CGRP receptor antagonist similarly inhibited contact hypersensitivity in wild-type mice. These observations provide compelling evidence that CGRP is a key regulator of cutaneous immunity through effects on ECs and suggest a novel pathway for potential therapeutic manipulation. |
