title: Regulation of interferon gamma signaling by suppressors of cytokine signaling and regulatory T cells.
abstract: Regulatory T cells (Tregs) play an indispensable role in the prevention of autoimmune disease, as interferon gamma (IFNγ) mediated, lethal auto-immunity occurs (in both mice and humans) in their absence. In addition, Tregs have been implicated in preventing the onset of autoimmune and auto-inflammatory conditions associated with aberrant IFNγ signaling such as type 1 diabetes, lupus, and lipopolysaccharide (LPS) mediated endotoxemia. Notably, suppressor of cytokine signaling-1 deficient (SOCS1(-/-)) mice also succumb to a lethal auto-inflammatory disease, dominated by excessive IFNγ signaling and bearing similar disease course kinetics to Treg deficient mice. Moreover SOCS1 deficiency has been implicated in lupus progression, and increased susceptibility to LPS mediated endotoxemia. Although it has been established that Tregs and SOCS1 play a critical role in the regulation of IFNγ signaling, and the prevention of lethal auto-inflammatory disease, the role of Treg/SOCS1 cross-talk in the regulation of IFNγ signaling has been essentially unexplored. This is especially pertinent as recent publications have implicated a role of SOCS1 in the stability of peripheral Tregs. This review will examine the emerging research findings implicating a critical role of the intersection of the SOCS1 and Treg regulatory pathways in the control of IFN gamma signaling and immune system function.
authors.affiliation: Department of Microbiology and Cell Science, University of Florida , Gainesville, FL , USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Larkin
authors.affiliation: Department of Microbiology and Cell Science, University of Florida , Gainesville, FL , USA.
authors.forename: Chulbul M
authors.initials: CM
authors.lastname: Ahmed
authors.affiliation: Department of Microbiology and Cell Science, University of Florida , Gainesville, FL , USA.
authors.forename: Tenisha D
authors.initials: TD
authors.lastname: Wilson
authors.affiliation: Department of Microbiology and Cell Science, University of Florida , Gainesville, FL , USA.
authors.forename: Howard M
authors.initials: HM
authors.lastname: Johnson
keywords: T cells; auto-immunity; inflammation; lupus; tolerance/suppression/anergy