title: Calcitonin gene-related peptide enhances experimental autoimmune encephalomyelitis by promoting Th17-cell functions.
abstract: T(h)17 cells, an inflammatory T helper cell subset, are involved in the pathogenesis of various inflammatory, autoimmune and allergic diseases. Recent evidence supports the idea that immune cell functions and the inflammatory response are finely regulated by various physiological substances. Calcitonin gene-related peptide (CGRP), a neuropeptide released from the sensory nerve endings, is one of these mediators. By binding to its receptor composed of receptor activity-modifying protein 1 (RAMP1) and calcitonin receptor-like receptor, CGRP modulates various immune cell functions, but the function of CGRP in T(h)17 cells is largely unknown. Here, we investigated the effect of CGRP signaling on T(h)17 cells and T(h)17 cell-mediated inflammation and observed that CGRP activates nuclear factor of activated T cells c2 through cAMP/PKA to increase IL-17 production in vitro. In vivo, IL-17 production is suppressed in RAMP1-deficient mice in the experimental autoimmune encephalomyelitis (EAE) model and RAMP1-deficient mice are completely resistant to EAE. Furthermore, T(h)17 cell function and EAE induction are also suppressed in T cell-specific RAMP1-deficient mice. Taken together, our findings indicate that CGRP promotes T(h)17 cell-mediated autoimmune inflammation through the regulation of IL-17 expression.
authors: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University Osaka 565-0871, Japan.
authors: Norihisa
authors: N
authors: Mikami
authors: Keiko
authors: K
authors: Watanabe
authors: Nagisa
authors: N
authors: Hashimoto
authors: Yayoi
authors: Y
authors: Miyagi
authors: Kaori
authors: K
authors: Sueda
authors: So-ichiro
authors: S
authors: Fukada
authors: Hiroshi
authors: H
authors: Yamamoto
authors: Kazutake
authors: K
authors: Tsujikawa
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology*; D058286:Calcitonin Receptor-Like Protein / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000276:immunology / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D050778:NFATC Transcription Factors / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D058262:Receptor Activity-Modifying Protein 1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D058286:Calcitonin Receptor-Like Protein; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; D010446:Peptide Fragments; C545505:Ramp1 protein, mouse; D058262:Receptor Activity-Modifying Protein 1; C445081:myelin oligodendrocyte glycoprotein (35-55); D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015740:Calcitonin Gene-Related Peptide