Lumican negatively controls the pathogenicity of murine encephalitic TH17 cells

Abstract

TH17 cells play an essential role in the development of both human multiple sclerosis and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, it is not well understood how the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation. In vitro, we found Lumican (Lum), an extracellular matrix protein, is selectively expressed by TH17 cells among tested murine TH subsets. Lum-deficiency leads to earlier onset and enhanced severity of experimental autoimmune encephalomyelitis. This enhanced disease in Lum-deficient mice is associated with increased production of IL-17 and IL-21 and enhanced TH17 cell apoptosis. Dysregulation in cytokine production appears to be specific to TH17 cells as TH1 and TH2 cell polarization and/or cytokine production were unaltered. Furthermore, adoptive transfer of MOG-specific TH17 cells derived from Lum-deficient mice led to earlier onset and increased severity of disease compared to controls highlighting a TH17 cell-intrinsic effect of Lum. Taken together, our results suggest that Lum negatively regulates encephalitic TH17 cells, implicating a potential therapeutic pathway in TH17 cell-mediated autoimmune and inflammatory diseases.

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