T-bet promotes the accumulation of encephalitogenic Th17 cells in the CNS

- The mechanism by which T-bet enhances Th17 cell encephalitogenicity is investigated.
- T-bet expression promotes the accumulation of myelin-reactive T cells in the CNS.
- T-bet modulates the pattern of homing molecules on myelin-reactive CD4 + T cells.
- T-bet might serve as a therapeutic target to block CNS homing of Th17 and Th1 cells.

T-bet enhances the encephalitogenicity of myelin-reactive CD4+ T cells, however its mechanism of action is unknown. In this study we show that T-bet confers a competitive advantage for the accumulation of IL-23 conditioned Th17 effector cells in the central nervous system (CNS). Impaired migration of T-bet deficient Th17 cells to the CNS is associated with altered expression of adhesion molecules and chemokine receptors on their cell surface. Our data suggest that therapeutic targeting of T-bet in individuals with Th17-mediated autoimmune demyelinating disease may inhibit inflammatory infiltration of the CNS and, hence, clinical exacerbations.

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