Deletion of the G2A receptor fails to attenuate experimental autoimmune encephalomyelitis

Autor: Roshni Srivastava, Janusz H. Kabarowski, Jillian E. Wohler, Sherry S. Smith, Brian W. Parks, Inga Osmers, Scott R. Barnum, Shaohua Yu
Rok vydání: 2008
Předmět:
CD4-Positive T-Lymphocytes
Encephalomyelitis
Autoimmune
Experimental
Time Factors
T cell
Encephalomyelitis
T-Lymphocytes
Immunology
chemical and pharmacologic phenomena
Cell Cycle Proteins
Biology
CD8-Positive T-Lymphocytes
medicine.disease_cause
Lymphocyte Activation
complex mixtures
Article
Autoimmunity
Receptors
G-Protein-Coupled
Interferon-gamma
Mice
parasitic diseases
medicine
Immunology and Allergy
Animals
Interferon gamma
IL-2 receptor
Cell Proliferation
Glycoproteins
Autoimmune disease
Mice
Knockout
Experimental autoimmune encephalomyelitis
hemic and immune systems
T lymphocyte
medicine.disease
bacterial infections and mycoses
Flow Cytometry
Peptide Fragments
Mice
Inbred C57BL
medicine.anatomical_structure
Neurology
Myelin-Oligodendrocyte Glycoprotein
Neurology (clinical)
Lymph Nodes
Gene Deletion
Spleen
medicine.drug
Zdroj: Journal of neuroimmunology. 207(1-2)
ISSN: 0165-5728
Popis: Lysophosphatidylcholine (LPC) is a chemotactic lysolipid produced during inflammation by the hydrolytic action of phospholipase A(2) 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 MOG(35-55) peptide. Disease severity was only moderately reduced in G2A(-/-) mice. Similar numbers of MOG(35-55) specific T cells were generated in secondary lymphoid organs of MOG(35-55)-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.
Databáze: OpenAIRE
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