Journal
INTERNATIONAL IMMUNOLOGY
Volume 24, Issue 11, Pages 681-691Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxs075
Keywords
calcitonin gene-related peptide; encephalomyelitis; experimental autoimmune; Th17 cell
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [22590062]
- Japan Chemical Industry Association (JCIA) Long-range Research Initiative (LRI)
- Osaka Foundation for Promotion of Clinical Immunology
- Grants-in-Aid for Scientific Research [22590062] Funding Source: KAKEN
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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.
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