Citation

Objective: To investigate the effects of targeting the high-affinity receptor for immunoglobulin E (FcRI), that plays a central role in allergic responses and is constitutively expressed on mast cells and basophils, in clinical disease and autoimmune T-cell response in experimental MS. Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein 3555. Anti-FcRI -chain antibody was administered intraperitoneally. CNS immunohistochemistry, flow cytometry analysis of immune cell populations, IgE and histamine serum concentration, immune cell proliferation, and cytokine measurement were performed. In BALB/c mice, EAE was induced by immunization with myelin proteolipid protein 185206. Results: Treatment with anti-FcRI antibody resulted in exacerbation of EAE and increased CNS inflammation in C57BL/6 mice. Treated mice displayed long-lasting complete depletion of basophils in the blood stream and peripheral lymphoid organs and increased antigen-induced immune cell proliferation and production of interferon-, interleukin (IL)-17, IL-6, and granulocyte-macrophage colony-stimulating factor. In BALB/c mice, which are T-helper (Th) 2 prone and resistant to EAE, treatment with anti-FcRI antibody restored susceptibility to EAE. Conclusion: Our observations that anti-FcRI antibody increases Th1 and Th17 responses against myelin antigen and exacerbates EAE suggest that FcRI, basophils, and possibly other FcRI-bearing cells that might be affected by this antibody play important roles in influencing the severity of CNS autoimmunity.