IL-11 antagonist suppresses Th17 cell-mediated neuroinflammation and demyelination in a mouse model of relapsing-remitting multiple sclerosis

Publication date: Available online 24 August 2018

Source: Clinical Immunology

Author(s): Xin Zhang, Nazanin Kiapour, Sahil Kapoor, Joseph R. Merrill, Yongjuan Xia, Woomi Ban, Stephanie M. Cohen, Bentley R. Midkiff, Valerie Jewells, Yen-Yu I. Shih, Silva Markovic-Plese

Abstract

IL-11 induced differentiation and expansion of Th17 cells in patients with early relapsing-remitting multiple sclerosis (RRMS). In mice with relapsing-remitting experimental autoimmune encephalomyelitis (RREAE), IL-11 exacerbated disease, induced demyelination in the central nervous system (CNS), increased the percentage of IL-17A⁺CD4⁺ Th17 cells in the CNS in the early acute phase, and up-regulated serum IL-17A levels and the percentage of IL-17A⁺CD4⁺ Th17 cells in lymph nodes, and IFN-γ⁺CD4⁺ T cells in spinal cord in the RR phase. IL-11 antagonist suppressed RREAE disease activities, inhibited IL-17A⁺CD4⁺ cell infiltration and demyelination in the CNS, and decreased the percentage of IL-17A⁺CD4⁺ T cells in peripheral blood mononuclear cells and ICAM1⁺CD4⁺ T cells in brain and SC. Diffusion Tensor Imaging indicated that IL-11 antagonist inhibited demyelination in several brain regions. We conclude that by suppressing Th17 cell-mediated neuroinflammation and demyelination, IL-11 antagonist can be further studied as a potential selective and early therapy for RRMS.

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