How do Th17 cells mediate autoimmune inflammation in the central nervous system?

Th17 cells were first discovered in the context of autoimmunity, but it is likely that this subset of T helper cells has its primary function in host defense of pathogens, such as particular fungi against which Th1 or Th2 responses are not protective. In the early days of Th17 research, a great deal of effort was made to prove the identity of Th17 cells as a distinct lineage of T helper cells independent of Th1 and Th2 cells. However, Th17 cells are increasingly considered as a plastic subset of T helper cells that can co-produce interleukin-17 with interferon-γ or interleukin-17 with interleukin-10 and then usurp T-bet or c-Maf as transcription factors that have been regarded as private to Th1 or Th2 cells, respectively. A coherent concept to explain the importance of Th17 cells in a series of autoimmune diseases including psoriasis, rheumatoid arthritis and multiple sclerosis is still missing. However, the prominent role of Th17 cell responses at epithelial surfaces (like the gut) where the discrimination between self and foreign is particularly challenging might contribute to the predominant Th17 skewing of autoreactive T cells when immune tolerance is broken. In the present review, some novel aspects on the generation and biological properties of Th17 cells including trafficking and effector functions with particular emphasis on autoimmunity in the central nervous system are highlighted.