IL-11 Induces Encephalitogenic Th17 Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Abstract

IL-11⁺CD4⁺ cells accumulate in the cerebrospinal fluid of patients with early relapsing-remitting multiple sclerosis (MS) and in active brain MS lesions. Mouse studies have confirmed a causal role of IL-11 in the exacerbation of relapsing-remitting experimental autoimmune encephalomyelitis (RREAE). Administration of IL-11 at the time of clinical onset of RREAE induced an acute exacerbation and increased clinical scores, which persisted during the entire course of the disease. IL-11 increased the numbers of spinal cord inflammatory foci, as well as the numbers of peripheral and CNS-infiltrating IL-17⁺CD4⁺ cells and IL-17A serum levels. Ag recall assays revealed that IL-11 induces IL-17A⁺, GM-CSF⁺, and IL-21⁺CD4⁺ myelin Ag-reactive cells. Passive transfer of these encephalitogenic CD4⁺ T cells induced severe RREAE with IL-17A⁺CCR6⁺ CD4⁺ and B cell accumulation within the CNS. Furthermore, passive transfer of nonmanipulated CNS-derived mononuclear cells from mice with RREAE after a single dose of IL-11 induced severe RREAE with increased accumulation of IL-17A⁺ and CCR6⁺ CD4⁺ cells within the CNS. These results suggest that IL-11 might serve as a biomarker of early autoimmune response and a selective therapeutic target for patients with early relapsing-remitting MS.