title: Jagged-1 signaling suppresses the IL-6 and TGF-β treatment-induced Th17 cell differentiation via the reduction of RORγt/IL-17A/IL-17F/IL-23a/IL-12rb1.
abstract: Jagged-1 signaling has recently been reported to be involved in the Th17 cell differentiation. However, little is known about its mechanisms. Soluble Jagged-1 was used to activate the Jagged-1-Notch signaling to interfere with the IL-6 and TGF-β-induced Th17 cell skewing. Genes relevant to the autoimmunity or inflammation were screened for the first time in this system by qPCR array for the differential expressions. The 18 genes out of 84, including Clec7a, Il12b, Il12rb1, Il12rb2, Csf3, Il15, Il17a, Il17f, Il17rc, Il17rd, Il17re, Il23a, Myd88, Socs1, Stat4, Stat5a, Sykb and Tbx21, were downregulated, but only Cxcl2, Cxcl12 and Mmp3 were upregulated. The expressions of the genes, Rorγt, Il17a, Il17f, Il12rb1 and Il23a, induced by simultaneous IL-6 and TGF-β treatment were significantly suppressed by Jagged-1, followed by the reduction of RORγt, IL-17A, and IL-17F. Consistent with the attenuation of RORγt, and the reduced production and secretion of IL-17A and IL-17F in the cell supernatant and the in situ stained cells, the number of CD4(+)IL-17(+) cells was also diminished. It is concluded that the Jagged-1-Notch signaling can suppress the IL-6 and TGF-β treatment-induced Th17 cell skewing through the attenuation of RORγt and, hence by, the down-regulation of IL-17A, IL-17F, IL-23a, and IL-12rb1.
authors: 1] Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China [2] Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China.
authors: Yuan
authors: Y
authors: Wang
authors: 1] Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China [2] Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China.
authors: Feiyue
authors: F
authors: Xing
authors: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors: Siqi
authors: S
authors: Ye
authors: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors: Jia
authors: J
authors: Xiao
authors: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors: Jingfang
authors: J
authors: Di
authors: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors: Shan
authors: S
authors: Zeng
authors: Department of Stomatology, Jinan University, Guangzhou 510632, China.
authors: Jing
authors: J
authors: Liu
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology*; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; D015850:Interleukin-6; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins
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