title: SOCS3 in immune regulation of inflammatory bowel disease and inflammatory bowel disease-related cancer.
abstract: Inflammatory bowel disease (IBD) has unclear pathogenesis and it is related to the increasing risk of developing colorectal cancer (CRC). Recent studies have uncovered the molecular mechanism of intracellular signaling pathways of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-6. The major transcription factors including STAT3 have been shown to play a major role in transmitting inflammatory cytokine signals to the nucleus. The suppressors of cytokine signaling (SOCS) 3 protein is the key physiological regulators of cytokine-mediated STAT3 signaling. As such it influences the development of inflammatory and malignant disorders like this associated with IBD. Here we review the complex function of SOCS3 in innate and adaptive immunity, different cell types (macrophages, neutrophils, dendritic cells, B cells, T cells and intestinal epithelial cells) and the role of SOCS3 on the pathogenesis of inflammatory bowel disease (IBD) and IBD-related cancer. Finally, we explore how this knowledge may open novel avenues for the rational treatment of IBD and IBD-related cancer.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands. yili1101@hotmail.com
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Colin
authors.initials: C
authors.lastname: de Haar
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.forename: C Janneke
authors.initials: CJ
authors.lastname: van der Woude
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology; D015179:Colorectal Neoplasms / Q000209:etiology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007249:Inflammation / Q000150:complications; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins