NDLI: Engagement of activated Notch signalling in collagen II-specific T helper type 1 (Th1)- and Th17-type expansion involving Notch3 and Delta-like1

Content Provider	PubMed Central
Author	Jiao, Z. Wang, W. Xu, H. Wang, S. Guo, M. Chen, Y. Gao, J.
Abstract	Our previous study demonstrated that T helper (Th) cells from patients with rheumatoid arthritis (RA) display an altered expression profile of Notch receptors and enhanced activation of Notch signalling. The aim of this study was to investigate the role of distinct Notch receptors and ligands in the activation and differentiation of collagen II (CII)-reactive Th cells upon antigen-specific restimulation. Spleen mononuclear cells (SMNCs) from CII-immunized DBA/1J mice were restimulated by culturing with CII. CII-specific proliferation and differentiation of T cells were determined by tritiated thymidine (3[H]-TdR) incorporation and flow cytometric analysis, respectively. The mRNA expression of Notch receptors and Hes1 was assessed by real-time polymerase chain reaction (PCR). There was a clear increase in the percentage of Th1 cells and Th17 cells after CII restimulation. No significant difference was observed in the percentage of regulation T cells (Treg) in SMNCs with or without CII restimulation. CII restimulation induced up-regulated transcript levels of Hes1 in CII-reactive CD4+ T cells. The mRNA level of Notch3 was also up-regulated significantly, while the levels of the other three Notch receptors were not increased. Inhibition of Notch signalling by N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) and Notch3 antibody decreased the collagen-specific T cell proliferation and attenuated Th1- and Th17-type responses, while treatment with Notch ligand Delta-like 1 promoted such a response. The present study demonstrates that Notch signalling is engaged in CII-specific Th1- and Th17-type expansion in which Notch3 and Delta-like1 were involved. Selective inhibition of Notch signalling mediated by Notch3 or Delta-like1 may offer a new strategy for the treatment of RA.
Related Links	http://dx.doi.org/10.1111/j.1365-2249.2010.04310.x
Ending Page	71
Page Count	6
Starting Page	66
File Format	PDF
ISSN	00099104
e-ISSN	13652249
Journal	Clinical and Experimental Immunology
Issue Number	1
Volume Number	164
Language	English
Publisher	Blackwell Science Inc
Publisher Date	2011-04-01
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Immunology Immunology and Allergy Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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