Effective immune responses require the activation and differentiation of lymphocytes. These processes are then followed by the timely elimination of the responding cells in order to restore immune homeostasis. Appropriate execution of these developmental programs is normally regulated by exposure…
more to different stimuli, which need to be appropriately interpreted as lymphocytes proceed along their differentiation pathway. Although the early steps in lymphocyte activation have been extensively studied, the mechanisms employed by lymphocytes to integrate the information provided by different signals are not fully characterized. Disturbances in this decision-making process may underlie the pathogenesis of many immune-mediated disorders like autoimmunity. The main goal of our laboratory is to dissect the basic molecular mechanisms employed by lymphocytes to appropriately integrate the information provided by distinct classes of activation stimuli. To address this question we have focused our studies on two factors that are highly expressed in lymphocytes, IRF-4 (Interferon Regulatory Factor 4) and IBP (IRF-4 Binding Protein). We have shown that IRF-4 and IBP receive inputs from multiple pathways and may thus potentially act as “integrators” of lymphocyte responses. Our studies have furthermore indicated that IRF-4 and IBP control a broad range of biological processes in lymphocytes, namely cytokine production, cytoskeletal dynamics and survival. Consistent with the notion that alterations in the expression/function of these “integrators” may lead to pathophysiological consequences, our recent studies have revealed that deletion of IBP leads to the spontaneous development of a systemic autoimmune disorder in mice that like human SLE preferentially affects the female gender.
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