Expression of Scavenger receptor A on antigen presenting cells is important for CD4⁺ T-cells proliferation in EAE mouse model

• Main Authors: Levy-Barazany Hilit, Frenkel Dan
• Format: Article
• Language: English
• Published: BMC 2012-06-01
• Series: Journal of Neuroinflammation
• Subjects: Scavenger receptor A; SRA; CD4⁺ T-cell; EAE; Multiple sclerosis; Macrophage; APC; Microglia; Astrocyte
• Online Access: http://www.jneuroinflammation.com/content/9/1/120

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by damage to the neuronal myelin sheath. One of the key effectors for inflammatory injury is the antigen-presenting cell (APC). The class A scavenger receptor (SRA), constitutively expressed by APCs, such as macrophages and dendritic cells in peripheral tissues and the CNS, was shown to play a role in the phagocytosis of myelin; however, the role of SRA in the development of experimental autoimmune encephalomyelitis (EAE) and autoimmune reaction in the periphery has not yet been studied.</p> <p>Methods</p> <p>We investigated EAE progression in wild-type (WT) vs. SRA^−/− mice using clinical score measurements and characterized CNS pathology using staining. Furthermore, we assessed SRA role in mediating anti myelin pro-inflammatory response in cell cultures.</p> <p>Results</p> <p>We discovered that EAE progression and CNS demyelination were significantly reduced in SRA^−/− mice compared to WT mice. In addition, there was a reduction of infiltrating peripheral immune cells, such as T cells and macrophages, in the CNS lesion of SRA^−/− mice, which was associated with reduced astrogliosis. Immunological assessment showed that SRA deficiency resulted in significant reduction of pro-inflammatory cytokines that play a major role in EAE progression, such as IL-2, IFN-gamma, IL-17 and IL-6. Furthermore, we discovered that SRA^−/− APCs showed impairments in activation and in their ability to induce pro-inflammatory CD4⁺ T cell proliferation.</p> <p>Conclusion</p> <p>Expression of SRA on APCs is important for CD4⁺ T-cells proliferation in EAE mouse model. Further studies of SRA-mediated cellular pathways in APCs may offer useful insights into the development of MS and other autoimmune diseases, providing future avenues for therapeutic intervention.</p>