Pituitary adenylyl cyclase-activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis
Abstract
Pituitary adenylyl cyclase-activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis Yossan-Var Tana, Catalina Abada, Robert Lopeza, Hongmei Donga, Shen Liua, Alice Leea, Rosa P. Gomarizb, Javier Lecetab, and James A. Wascheka,1 aSemel Institute/Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and bDepartamento de Biología Celular, Facultad de Biología, Universidad Complutense, 28040 Madrid, Spain Edited by Susan E. Leeman, Boston University School of Medicine, Boston, MA, and approved December 16, 2008 (received for review December 3, 2008) Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a widely expressed neuropeptide originally discovered in the hypothalamus. It closely resembles vasoactive intestinal peptide (VIP), a neuropeptide well known to inhibit macrophage activity, promote Th2-type re- sponses, and enhance regulatory T cell (Treg) production. Recent studies have shown that administration of PACAP, like VIP, can attenuate dramatically the clinical and pathological features of mu- rine models of autoimmune diseases such as experimental autoim- mune encephalomyelitis (EAE) and collagen-induced arthritis. How- ever, specific roles (if any) of endogenous VIP and PACAP in the protection against autoimmune diseases have not been explored. Here, we subjected PACAP-deficient mice to myelin oligodendrocyte glycoprotein (MOG35–55)-induced EAE. MOG immunization of PACAP- deficient mice triggered heightened clinical and pathological manifes- tations of EAE compared to wild-type mice. The increased sensitivity was accompanied by enhanced mRNA expression of proinflammatory cytokines (TNF, IL-6, IFN-, IL-12p35, IL-23p19, and IL-17), chemokines (MCP-1/CCL2, MIP-1/CCL3, and RANTES/CCL5), and chemotactic factor receptors (CCR1, CCR2, and CCR5), but downregulation of the anti- inflammatory cytokines (IL-4, IL-10, and TGF-) in the spin
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Symptom Clusters
Cited By (4)
- Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1British Journal of Pharmacology · 2012
- Exploring the Pro-Phagocytic and Anti-Inflammatory Functions of PACAP and VIP in Microglia: Implications for Multiple SclerosisInternational Journal of Molecular Sciences · 2022
- VIP and PACAP: recent insights into their functions/roles in physiology and disease from molecular and genetic studiesCurrent Opinion in Endocrinology Diabetes and Obesity · 2011
- Inhaled vasoactive intestinal peptide exerts immuno-regulatory effects in sarcoidosisAmerican Journal of Respiratory and Critical Care Medicine · 2010
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