Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease

It is unclear whether TGF-beta, a critical differentiation factor for T cells producing interleukin 17 ( T-H-17 cells), is required for the initiation of experimental autoimmune encephalomyelitis ( EAE) in vivo. Here we show that mice whose T cells cannot respond to TGF-b signaling lack T-H-17 cells and do not develop EAE despite the presence of T helper cell type 1 infiltrates in the spinal cord. Local but not systemic antibody blockade of TGF-beta prevented T-H-17 cell differentiation and the onset of EAE. The pathogen stimulus zymosan, like mycobacterium, induced T-H-17 cells and initiated EAE, but the disease was transient and correlated with reduced production of interleukin 23. These data show that TGF-beta is essential for the initiation of EAE and suggest that disease progression may require ongoing chronic inflammation and production of interleukin 23.