Master regulator not so masterful

M
O’Connor RA, Cambrook H, Huettner K, Anderton SM T-bet is essential for Th1-mediated, but not Th17-mediated, CNS autoimmune disease. Eur J Immunol. 2013 Jul 23. doi: 10.1002/eji.201343689. [Epub ahead of print]
T-bet is essential for establishing Th1-mediated inflammation but is not required to drive IL-23-induced GM-CSF production, or Th17-mediated autoimmune inflammation.


Highly polarized Th17 cells induce EAE via a T-bet independent mechanism.Grifka-Walk HM, Lalor SJ, Segal BM. Eur J Immunol. 2013 Jul 23. doi: 10.1002/eji.201343723. [Epub ahead of print]
The “master regulator” transcription factor, T-bet, is also not universally required for encephalitogenicity.


The search for the encephalitogenic factor driving pathogenic T cells in autoimmune diseases has proven to be a long and difficult mission, which is not yet completed. The importance of the transcription factor T-bet, previously shown to be essential for the induction of autoimmune disease in mice, is challenged. It is reported that that T-bet is not mandatory for T cells to cause experimental autoimmune encephalomyelitis (EAE). It was found that mice that lack T-bet 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 and maybe a target has gone begging.


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