Deletion of the G2A receptor fails to attenuate experimental autoimmune encephalomyelitis

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.