Deletion of the G2A receptor fails to attenuate experimental autoimmune encephalomyelitis

• Published in: Journal of neuroimmunology 2009-02, Vol.207 (1), p.18-23
• Main Authors: Osmers, Inga, Smith, Sherry S, Parks, Brian W, Yu, Shaohua, Srivastava, Roshni, Wohler, Jillian E, Barnum, Scott R, Kabarowski, Janusz H.S
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - physiology; Cell Proliferation - drug effects; Chemotaxis; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - immunology; Flow Cytometry - methods; G2A; Gene Deletion; Glycoproteins - adverse effects; Interferon-gamma - metabolism; Lymph Nodes - drug effects; Lymph Nodes - immunology; Lymph Nodes - pathology; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lysophosphatidylcholine; Mice; Mice, Inbred C57BL; Mice, Knockout; Multiple sclerosis; Myelin-Oligodendrocyte Glycoprotein; Neurology; Peptide Fragments - adverse effects; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - physiology; Spleen - cytology; Spleen - immunology; Spleen - pathology; T lymphocyte; T-Lymphocytes - immunology; Time Factors
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2008.11.008

Abstract Lysophosphatidylcholine (LPC) is a chemotactic lysolipid produced during inflammation by the hydrolytic action of phospholipase A2 enzymes. LPC stimulates chemotaxis of T cells in vitro through activation of the G protein-coupled receptor, G2A. This has led to the proposition that G2A contributes to the recruitment of T cells to sites of inflammation and thus promotes chronic inflammatory autoimmune diseases associated with the generation and subsequent tissue infiltration of auto-antigen-specific effector T cells. However, one study suggests that G2A may negatively regulate T cell proliferative responses to antigen receptor engagement and thereby attenuates autoimmunity by reducing the generation of autoreactive T cells. To address the relative contribution of these G2A-mediated effects to the pathophysiology of T cell-mediated autoimmune disease, we examined the impact of G2A inactivation on the onset and severity of murine experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Wild type (G2A+/+ ) and G2A-deficient (G2A−/− ) C57BL/6J mice exhibited a similar incidence and onset of disease following immunization with MOG35–55 peptide. Disease severity was only moderately reduced in G2A−/− mice. Similar numbers of MOG35–55 specific T cells were generated in secondary lymphoid organs of MOG35–55 -immunized G2A+/+ and G2A−/− mice. Comparable numbers of T cells were detected in spinal cords of G2A+/+ and G2A−/− mice. We conclude that the proposed anti-proliferative and chemotactic functions of G2A are not manifested in vivo and therefore therapeutic targeting of G2A is unlikely to be beneficial in the treatment of MS.