| First Author | Roach T | Year | 2024 |
| Journal | Mol Immunol | Volume | 165 |
| Pages | 1-10 | PubMed ID | 38056350 |
| Mgi Jnum | J:354872 | Mgi Id | MGI:7567206 |
| Doi | 10.1016/j.molimm.2023.11.008 | Citation | Roach T, et al. (2023) Regulation of the STAT3 pathway by lupus susceptibility gene Pbx1 in T cells. Mol Immunol 165:1-10 |
| abstractText | Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which poorly characterized genetic factors lead to the production of proinflammatory or autoreactive T cells. Pre-B cell leukemia homeobox 1 (PBX1) is a transcription factor whose dominant negative isoform (PBX1-D) is overexpressed in the CD4(+) T cells of SLE patients and lupus-prone mice. Pbx1-D overexpression favors the expansion of proinflammatory T cells and impairs regulatory T (Treg) cell development. Here we show that Pbx1 deficiency and Pbx1-D overexpression decreased STAT3 expression and activation in T cells. Accordingly, Pbx1 deficiency in T cells and Pbx1-D overexpression reduced STAT3-dependent T(H)17 cell polarization in vitro, but it had no effect in vivo at steady state. STAT3-dependent follicular helper T (T(FH)) cell polarization in vitro and splenic T(FH) cell frequency were not affected by either Pbx1 deficiency or Pbx1-D overexpression. Pbx1 deficiency also increased the expression of cell cycle arrest and pro-apoptotic genes, with an increased apoptosis in T cells. Our results suggest a complex interplay between PBX1 and STAT3, which may contribute to lupus pathogenesis through dysregulation of the cell cycle and apoptosis. |
