SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress
| Autor: | Juil Kim, Seong-Hwan Park, Hye Jin Choi, Ki Hyung Kim, Kee Hun Do, Yuseok Moon |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Chromatin Immunoprecipitation
Blotting Western Immunology Suppressor of Cytokine Signaling Proteins Real-Time Polymerase Chain Reaction Transfection Proinflammatory cytokine Mice Downregulation and upregulation Stress Physiological B-Cell Activating Factor medicine Animals Humans Immunology and Allergy STAT1 SOCS3 B-cell activating factor B cell Microscopy Confocal biology Reverse Transcriptase Polymerase Chain Reaction Flow Cytometry Cell biology Mice Inbred C57BL Enterocytes medicine.anatomical_structure Suppressor of Cytokine Signaling 3 Protein biology.protein Female Signal transduction Ribosomes Signal Transduction |
| Zdroj: | The Journal of Immunology. 190:6501-6510 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1203004 |
| Popis: | 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-γ. Furthermore, IFN-γ triggered JAK/STAT1 signals via the cytokine receptor, which contributed to epithelial BAFF upregulation. In terms of signaling intervention, ribosomal insult attenuated IFN-γ–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. |
| Databáze: | OpenAIRE |
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