title: T-bet or not T-bet: taking the last bow on the autoimmunity stage.
abstract: The search for the encephalitogenic factor driving pathogenic T cells in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis (MS), and psoriasis has proven to be a long and difficult mission, which is not yet completed. In this issue of the European Journal of Immunology, the importance of the transcription factor T-bet, previously shown to be essential for the induction of autoimmune disease in mice, is challenged. Two independent groups, O'Connor et al. [Eur. J. Immunol. 2013. 43:2818-2823] report] and Grifka-Walk et al. [Eur. J. Immunol. 2013. 43:2824-2831], report that T-bet is not mandatory for T cells to cause experimental autoimmune encephalomyelitis (EAE), which serves as a paradigmatic T-cell-mediated autoimmune disease. Both groups found that T-bet KO mice were fully susceptible to develop EAE, both after immunization with self-antigen and after adoptive transfer of IL-23-polarized autoaggressive T cells. T-bet deficiency mediated the loss of IFN-γ expression but retained or even enhanced GM-CSF and IL-17 production by central nervous system (CNS)-infiltrating T cells. These findings indicate that we have lost the last transcriptional regulator previously held to be required for the generation of autoimmune pathogenic T cells.
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Spath
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: Autoimmunity; EAE; GM-CSF; IL-17; IL-23; T-bet; Transcription factors