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Runx transcription factors help dictate the fate of T cells as they become CD4+ or CD8+ T cells in the thymus, and Th1 or Th17 cells in the periphery. Now, according to Bruno et al., Runx proteins also guide regulatory T (T reg) cell fate.
Runx proteins have been shown to bind to the canonical T reg cell transcription factor Foxp3. Together, the two regulate (and primarily inhibit) the expression of target genes, such as the Th17-promoting transcription factor Ror-γt. Now Bruno and colleagues reveal that Runx proteins also help induce and maintain Foxp3 expression in mature CD4+ T cells.
Inducible T reg cells relied on Runx proteins to express Foxp3. Blocking the proteins reduced the number of these cells, and ablating an indispensable subunit of Runx protein complexes, Cbfb, diminished Foxp3 expression in natural T reg cells. Runx proteins bound directly to the Foxp3 promoter in T reg cells, but not in naive CD4+ T cells because of locus inaccessibility.
Another group recently reported that Runx/Cbfb complexes control the expression of Foxp3 in natural T reg cells in vivo. Without Cbfb, mice were susceptible to autoimmune disease. However, this study did not investigate a role for Runx proteins in T reg cell induction.
The relative contributions of Runx1 and Runx3 to Foxp3 regulation remain to be dissected. And because Runx proteins interact with so many genes, the authors are also curious to know how else these proteins may fine-tune T reg cell function.