Table 2.
Summary of PBX1 functions in immune cells.
| Model | PBX1 context | Mechanistic insights | Function/Phenotype | Related disease | Reference |
|---|---|---|---|---|---|
| CD4+ effector T cells | |||||
| B6.Sle1a.1 mice | Pbx1 lupus allele in Sle1a.1 interval | Increased CD4+ T cell proliferation; expansion of activated and autoreactive CD4+ T cells that support chromatin-specific B cell responses | Autoantibody production; increased inflammatory activity of effector CD4+ T cells | SLE; T cell induced colitis | (29) |
| Cd4-Pbx1-d Tg mice | T cell-specific Pbx1-d overexpression | Increases IL-21 production; promotes Tfh differentiation in an antigen-specific and T cell intrinsic manner and CD4+ T cell localization into B cell follicles | Production of lupus-associated autoantibodies; increased severity of T-cell-mediated colitis | SLE; T cell induced colitis | (51) |
| Bone-marrow transfer into Ldlr−/− mice + high-fat diet | T cell-specific Pbx1-d overexpression | Increased cardiovascular infiltrate and expansion of proinflammatory CD4+ T cells; increased Tfh cell frequency | Worsened atherosclerosis; higher autoantibody production | Atherosclerosis | (53) |
| B6.Sle1a.1 mice; Cd4-Pbx1-d Tg mice | T cell-specific Pbx1-d overexpression | Elevated expression of CD44 | Increased T cell activation | SLE | (29, 47) |
| Cd4-Pbx1−/− and Cd4-Pbx1-d Tg mice | T cell-specific Pbx1 knock-out/T cell specific Pbx1-d overexpression | Decreased STAT3 activation | Reduced Th17 polarization | SLE | (58) |
| Cd4-Pbx1−/−mice | T cell-specific Pbx1 knock-out | Increased Cdkn1a and Bax expression; decreased Bcl2 expression. | Reduced CD4+ T cell frequency, with early apoptosis | SLE | (58) |
| Tregs | |||||
| Human SLE; B6.Sle1a.1 mice; Pbx1-d Tg mice | Pbx1-d overexpression | Impaired TGF-β/RA-dependent Treg induction | Decreased Treg differentiation and suppressive capacity; increased non-suppressive CD25− Tregs | SLE; EAE | (30, 51, 66) |
| Foxp3-Pbx1−/− mice; Cd4-Pbx1-d Tg mice; combined models | Treg-specific Pbx1 knock-out; T cell-specific Pbx1-d overexpression | Preferential PBX1 expressed in Tregs among CD4+ T cells; decreased pTreg differentiation, stability and function; increased ex-Treg generation | Impaired suppressive capacity in induced lupus model; enhanced humoral/autoimmune responses | SLE; T cell induced colitis | (46) |
| Foxp3-Pbx1 −/− mice | Treg-specific Pbx1 knock-out | Reduced Rtkn2 expression in Tregs | Reduced Treg proliferation | SLE | (46) |
| Cd4-Pbx1-d Tg and B6.Sle1a.1 mice | T cell-specific Pbx1-d overexpression | Increased miR-10a, miR-21 and miR-155 expression | Pbx1-d–associated microRNA dysregulation may promote Treg dysfunction and lupus autoimmunity | SLE | (51) |
| B cells | |||||
| Human SLE; lupus-prone mice; Cd19- Pbx1−/− mice | B cell-specific Pbx1 knock-out | Increased E2f2 and decreased Cdkn1a, Bax, Bbc3 expression | Increased B cell survival and proliferation; enhanced humoral responses and autoantibody production | SLE | (31) |
| NK cells | |||||
| Vav1-Pbx1−/− mice | HSC-specific Pbx1 knock-out | Decreased Nfil3 expression | Impaired NK cell development | — | (45, 81) |
| Ncr1-Pbx1 −/− mice | NK-specific Pbx1 knock-out | Increased Lcn2 expression | Increased neutrophil/macrophage recruitment; fetal growth restriction | URSA | (82) |
| Pbx1 silencing NK cells | Pbx1 siRNA NK cells | Myeloma-derived exosome transmitted NEAT1 recruited EZH2 to suppress PBX1 | Inhibited the proliferation and activity of NK cells, promoting tumor immune escape | Multiple myeloma | (83) |
| Macrophages | |||||
| Macrophages derived from Pbx1+/− E14.5 embryonic liver; Lysm-Risp−/− mice | PBX1 activity | Promotes Il10 transcription during efferocytosis | Promotes anti-inflammatory responses and tissue repair | Inflammation resolution; tissue injury | (86, 87) |