NDLI: SOCS3 regulates BAFF in human enterocytes under ribosomal stress.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Choi, Hye Jin Kim, Juil Kim, Ki-Hyung Do, Kee Hun Park, Seong-Hwan Moon, Yuseok
Description	Country affiliation: South Korea Author Affiliation: Do KH ( Laboratory of Mucosal Exposome and Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan 626-870, South Korea.)
Abstract	Although the activation of B cells in the gastrointestinal tract is of great importance in the context of immunity to pathogens and mucosal inflammatory diseases, little is known about the mechanisms responsible for the local activation of B cells in the subepithelial area of the intestine. Epithelium-derived BAFF is the major modulator of B cell development and Ig class switching. The present study was performed to address the molecular mechanism of BAFF expression in gut epithelial cells in the presence of proinflammatory stimuli. Inflammation-induced BAFF expression in mucosal epithelial cells might be responsible for diverse mucosa-associated diseases linked to intestinal inflammation and autoimmunity. Although BAFF was marginally expressed in unstimulated epithelial cells, BAFF mRNA was significantly upregulated by proinflammatory IFN-Î³. Furthermore, IFN-Î³ triggered JAK/STAT1 signals via the cytokine receptor, which contributed to epithelial BAFF upregulation. In terms of signaling intervention, ribosomal insult attenuated IFN-Î³-activated JAK/STAT signal transduction and subsequent BAFF induction in gut epithelial cells. Ribosomal insults led to the superinduction of SOCS3 by enhancing its mRNA stability via HuR RNA-binding protein. Upregulated SOCS3 then contributed to the blocking of the JAK/STAT-linked signal, which mediated BAFF suppression by ribosomal stress. All of these findings show that ribosomal stress-induced SOCS3 plays a novel regulatory role in epithelial BAFF production, suggesting that epithelial ribosomal dysfunction in association with SOCS3 may be a promising therapeutic point in BAFF-associated human mucosal diseases.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	B-cell Activating Factor Metabolism Enterocytes Signal Transduction Physiology Stress, Physiological Suppressor Of Cytokine Signaling Proteins Animals Immunology Blotting, Western Chromatin Immunoprecipitation Flow Cytometry Mice Mice, Inbred C57bl Microscopy, Confocal Real-time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Ribosomes Pathology Transfection Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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