Tenascin-C deficiency protects mice from experimental autoimmune encephalomyelitis

- Number of Th1 cells is reduced in MOG35-55-imunized mice.
- Ability of Th17 cells to produce interleukin-17 is inhibited in MOG35-55-imunized mice.
- TnC-deficient mice are protected from EAE.
- There is no general immunosuppression in TnC-deficient mice.

The extracellular matrix glycoprotein tenascin-C (TnC) has been increasingly appreciated as a molecule susceptibly reacting to abnormalities in the mammalian immune system. TnC expression is elevated in inflamed tissues outside the immune system, but also in lymphoid organs. It participates in the promotion of inflammatory responses. Here, the role of TnC in a paradigm of CNS autoimmunity was investigated. Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, was induced in mice deficient in TnC (TnC−/− mice). Amelioration of EAE was observed in these mice in comparison to their wild-type (TnC+/+) littermates. Since T helper (Th)1 and Th17 cells play a dominant role in the pathogenesis of EAE, these cells were investigated in addition to analyzing locomotor functions and pro-inflammatory cytokine levels. Smaller numbers of interferon-gamma-producing Th1 cells and reduced ability of Th17 cells to produce interleukin-17 were observed in spleens of TnC−/− mice challenged by immunization with the myelin associated glycoprotein (MOG) when compared to TnC+/+ mice. There was no difference in Th1 and Th17 responses in non-immunized TnC−/− and TnC+/+ mice, thus excluding generalized immunosuppression in TnC−/− mice. These results show that TnC is important for the pathogenesis of CNS autoimmunity and that its deficiency interferes with Th1 and Th17 encephalitogenic potentials.