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Citations to this article

Loss of IRF-4–binding protein leads to the spontaneous development of systemic autoimmunity
Jessica C. Fanzo, … , Steven Greenberg, Alessandra B. Pernis
Jessica C. Fanzo, … , Steven Greenberg, Alessandra B. Pernis
Published March 1, 2006
Citation Information: J Clin Invest. 2006;116(3):703-714. https://doi.org/10.1172/JCI24096.
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Research Article Immunology

Loss of IRF-4–binding protein leads to the spontaneous development of systemic autoimmunity

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Abstract

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.

Authors

Jessica C. Fanzo, Wen Yang, So Young Jang, Sanjay Gupta, Qinzhong Chen, Ayesha Siddiq, Steven Greenberg, Alessandra B. Pernis

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Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2014 2013 2012 2011 2010 2009 2008 2007 Total
Citations: 1 1 1 2 4 3 4 1 3 2 1 2 5 1 5 5 5 1 47
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