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

Abstract

IL-11+CD4+ cells accumulate in the cerebrospinal fluid (CSF) of patients with early relapsing remitting multiple sclerosis (RRMS) and in the active brain MS lesions. Mouse studies have confirmed a causal role of IL-11 in the exacerbation of RR experimental autoimmune encephalomyelitis (EAE). 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 increased IL-17A serum levels. Antigen recall assays revealed that IL-11 induces IL-17A+, GM-CSF+ and IL-21+CD4+ myelin antigen-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 as a selective therapeutic target for patients with early RRMS.

Gut microbiota regulate tumor metastasis via circRNA/miRNA networks

“…For IL-11 administration, 63 6–8 mice per group were i.p. injected daily with either recombinant mouse IL-11 (0.5 μg/mouse) (Peprotech), 63 or control vehicle (PBS). The mice were monitored until the mice were sacrificed, followed with metastasis evaluation and histological studies.…”

“…For ABX mice models, mice were kept in specific pathogen-free (SPF) conditions and divided into two groups: a. SPF group; b. ABX group (Three weeks after drinking water with broad-spectrum antibiotics (ABX), followed with tumor cells being injected into C57BL/6 mice via tail vein, and ABX drinking water was continued until the mice were sacrificed. 3 For IL-11 administration, 63 6-8 mice per group were i.p. injected daily with either recombinant mouse IL-11 (0.5 μg/mouse) (Peprotech), 63 or control vehicle (PBS).…”

“…For the cell experiments including FACS analysis, LLC or melanoma B16-F10 cells were cultured in the absence or presence of IL-11 (Peprotech) (100 ng/ml) at different time points. 63…”

The Role of gp130 Cytokines in Tuberculosis

“…Thus, overexpression of IL-11 drives lymphocytic inflammation and fibrotic tissue remodeling in the murine airways [ 109 ] as well as heart and kidney fibrosis in mice [ 110 ]. Moreover, IL-11 is also involved in the recruitment of neutrophils to sites of inflammation or infection [ 111 , 112 ]. Most recently, IL-11 was demonstrated to promote the differentiation of TH17 cells in patients with multiple sclerosis (MS) and during relapsing-remitting experimental autoimmune encephalomyelitis (RREAE) [ 112 ].…”

Fibroblasts as an Alternative to Mesenchymal Stem Cells with Successful Treatment and Immune Modulation in EAE Model of Multiple Sclerosis

“…It is known Treg cells are reciprocal cells to Th17 cells, and it is also known the Th17 CD4 T cell subsets plays a major role in pathology of EAE as well as numerous other autoimmune disorders in man and mice (69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79). Accordingly, we assessed the IL-17 mediated pathway in vitro and in vivo.…”