The increased expression of IL-23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity
Autor: | Zhanju Liu, Hui Lin, Jiaming Qian, Praveen K. Yadav, Jingling Su, Maochun Tang, Xingpeng Wang, Jifeng Yu, Chi Chen, Ping-Chang Yang, Xiaorong Xu |
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Rok vydání: | 2011 |
Předmět: |
Adult
Male Cellular differentiation medicine.medical_treatment T cell Lymphocyte Immunology Blotting Western Apoptosis Biology Lymphocyte Activation Proinflammatory cytokine Immunoenzyme Techniques Crohn Disease medicine Immunology and Allergy Humans Lymphocytes RNA Messenger Intestinal Mucosa Cells Cultured Lamina propria Mucous Membrane Reverse Transcriptase Polymerase Chain Reaction Interleukin-17 Cell Differentiation Cell Biology Flow Cytometry Killer Cells Natural Cytokine medicine.anatomical_structure Case-Control Studies Interleukin-23 Subunit p19 Cytokines Interleukin-2 Th17 Cells Tumor necrosis factor alpha Colitis Ulcerative Female CD8 |
Zdroj: | Journal of leukocyte biology. 89(4) |
ISSN: | 1938-3673 |
Popis: | This study analyzed IL-23p19 expression in inflamed mucosa of IBD and the role in the induction of IEL and NK cell activation as well as Th17 cell differentiation. Expression of IL-23p19 was performed by immunohistochemistry and quantitative real-time PCR. Expression of IL-23R was assessed by flow cytometry. Cytolytic activities of IEL and NK cells by IL-23 were determined by a standard 51Cr-release assay. Cytokine levels were analyzed by ELISA and quantitative real-time PCR. Expression of IL-23p19 was increased significantly in inflamed mucosa of CD compared with that in UC and healthy controls. Double-staining confirmed that IL-23p19+ cells were mainly CD68+ macrophages/DCs. IL-23R+ cells were increased significantly in PB- and LP-CD4+ and -CD8+ T and NK cells. IL-23 markedly promoted IBD IEL and NK cell activation and cytotoxicity and triggered IBD PB- and LP-T cells to secrete significantly higher levels of IFN-γ, TNF, IL-2, and IL-17A compared with controls. Importantly, IL-23 promoted IBD PB- or LP-CD4+ T cells to differentiate into Th17 cells, characterized by increased expression of IL-17A and RORC. Anti-TNF treatment could markedly reduce IL-23 expression and Th17 cell infiltration in inflamed mucosa of CD patients. These data indicate that IL-23 is highly expressed in inflamed mucosa of IBD and plays an important role in the induction of IEL, NK, and T cell activation, proinflammatory cytokine secretion, and Th17 cell differentiation. Targeted therapy directed against IL-23p19 may have a therapeutic role in treatment of IBD. |
Databáze: | OpenAIRE |
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