Crosstalk between chemokines and neuronal receptors bridges immune and nervous systems.
Chemokine receptors, a family of Gi protein-coupled receptors responsible for cell migration, are widely expressed by cells of immune and nervous systems. Activation of receptors on the surface of leukocytes, such as opioid, vasoactive intestinal peptide, or adenosine receptors, often has inhibitory effects on chemokine receptors by a mechanism termed heterologous desensitization, resulting in suppression of immune responses. Conversely, activation of chemokine receptors also induces heterologous desensitization of mu-opioid receptors (MOR), a class of key analgesic receptors on neurons. Furthermore, prior exposure of neuronal cells to chemokine treatment enhances the sensitivity of transient receptor potential vanilloid 1 (TRPV1), a heat- and ligand-gated calcium channel, which is critical for sensing of pain. Consequently, during inflammation, activation of chemokine receptors on neurons contributes to hyperalgesia by inhibiting MOR and concomitantly sensitizing TRPV1 via Gi protein-mediated signaling pathways. These observations suggest that the crosstalk between chemokine receptors and neuropeptide membrane receptors serves as a bridge between the immune and nervous systems.
Zhang
Ning
N
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, Building 560, Room 21-89A, Frederick, MD 21702-1201, USA.
Oppenheim
Joost J
JJ
D000818:Animals; D018925:Chemokines / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000276:immunology*; D009420:Nervous System / Q000276:immunology*; D009474:Neurons / Q000276:immunology* / Q000378:metabolism; D010146:Pain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D020239:Receptor Cross-Talk / Q000276:immunology*; D043562:Receptors, G-Protein-Coupled / Q000276:immunology / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000276:immunology* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000276:immunology / Q000378:metabolism; D050916:TRPV Cation Channels / Q000276:immunology / Q000378:metabolism
D018925:Chemokines; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D017450:Receptors, Opioid, mu; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human