Pbx1 as a regulator of T-cell fate in autoimmunity

Pbx1 is a highly conserved transcription factor that regulates cell fate, proliferation, and apoptosis in multiple cell types, including stem cells and lineage precursors, and mature immune cells. The expression of a novel dominant-negative splice isoform of Pbx1, as well as a non-coding polymorphism near its 3' end in T cells and B cells, respectively, have been associated with susceptibility to systemic lupus erythematosus. This review, focused on T cells, presents the evidence that Pbx1 regulates the balance between regulatory and effector CD4⁺ T cells, with the lupus-associated dominant-negative isoform shifting toward the latter. The review also summarizes what is known about Pbx1 in B cells, NK cells and myeloid cells. Finally, evidence for a potential role of Pbx1 in the metabolic regulation of immune cells is reviewed.