title: Jagged-1-HES-1 signaling inhibits the differentiation of TH17 cells via ROR gammat.
abstract: Notch signaling plays an important role in differentiation of T cells. However, little is known as to action of it in differentiation of Th17 cell subset. In this study, a soluble Jagged-1/Fc chimera protein (Jagged-1) was directly used to activate Jagged-1-Notch signaling, while Hes-1-targeting siRNA was used to knock down Hes-1 gene to investigate effect of Jagged-1-Hes-1 signaling on the differentiation of CD4+ T cells into Th17 cells. The results showed that Jagged-1 could promote the expression of Hes-1 and Deltex-1 mRNAs and the expression of NICD, Hes-1 and Deltex-1 proteins, which might be significantly blocked by DAPT, a specific inhibitor of Notch signaling. Jagged-1-Hes-1 signaling resulted in the markedly decreased in situ expression of RORgammat in the CD4+ T cells induced by IL-6 plus TGF-ß. Flow cytometric analysis showed the reduction of IL-17 production in CD4+ T cells by Jagged-1, but the enhancement of it by Hes-1-targeting siRNA. The level of IL-10 produced by the treated cells was also enhanced, whereas the expression of IL-17 was prominently attenuated, which could be offset by anti-Jagged-1 antibody or DAPT. The results indicate that Jagged-1-Hes-1 signaling can suppress the skewing of CD4+ T cells toward Th17 cells via RORgammat, for which Hes-1 may be crucial.
authors.affiliation: Department of Immunobiology, Jinan University, Guangzhou, China.
authors.forename: P
authors.initials: P
authors.lastname: You
authors.forename: F
authors.initials: F
authors.lastname: Xing
authors.forename: C
authors.initials: C
authors.lastname: Mao
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Di
authors.forename: S
authors.initials: S
authors.lastname: Zeng
authors.forename: J
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020381:Interleukin-17 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051880:Receptors, Notch / Q000737:chemistry / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects; D058504:Th17 Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000072056:Transcription Factor HES-1; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; D015850:Interleukin-6; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; D016212:Transforming Growth Factor beta; D044767:Ubiquitin-Protein Ligases; C489734:Hes1 protein, mouse; C000606274:Jag1 protein, mouse; C104035:Dtx1 protein, mouse