| First Author | Fanzo JC | Year | 2006 |
| Journal | J Clin Invest | Volume | 116 |
| Issue | 3 | Pages | 703-14 |
| PubMed ID | 16470246 | Mgi Jnum | J:106469 |
| Mgi Id | MGI:3618636 | Doi | 10.1172/JCI24096 |
| Citation | Fanzo JC, et al. (2006) Loss of IRF-4-binding protein leads to the spontaneous development of systemic autoimmunity. J Clin Invest 116(3):703-14 |
| abstractText | IFN regulatory factor 4-binding (IRF-4-binding) protein (IBP) is a novel type of activator of Rho GTPases that is recruited to the immunological synapse upon TCR stimulation. Here we demonstrate that loss of IBP leads to the spontaneous development of a systemic autoimmune disorder characterized by the accumulation of effector/memory T cells and IgG+ B cells, profound hypergammaglobulinemia, and autoantibody production. Similar to human SLE, this syndrome primarily affects females. T cells from IBP-deficient mice are resistant to death in vitro as well as in vivo and exhibit selective defects in effector function. In the absence of IBP, T cells respond suboptimally to TCR engagement, as demonstrated by diminished ERK1/2 activation, decreased c-Fos induction, impaired immunological synapse formation, and defective actin polymerization. Transduction of IBP-deficient T cells with a WT IBP protein, but not with an IBP mutant lacking the Dbl-like domain required for Rho GTPase activation, rescues the cytoskeletal defects exhibited by these cells. Collectively, these findings indicate that IBP, a novel regulator of Rho GTPases, is required for optimal T cell effector function, lymphocyte homeostasis, and the prevention of systemic autoimmunity. |
