Notch signalling regulates cytokine production by CD8+ and CD4+ T cells.
The Notch signalling pathway regulates several aspects of cellular differentiation such as T lineage commitment and effector functions on peripheral T cells; however, there is limited information regarding Notch receptor expression on different T cell subsets and the putative role of the different receptors on T cell effector function. Here, we studied the protein expression of Notch receptors on murine T cells in vitro and in vivo and analysed the role of the Notch pathway in cytokine production by CD4+ and CD8+ T cells. We found that resting CD4+ and CD8+ T cells do not express Notch receptors, but they upregulate Notch 1 and Notch 2 shortly after in vitro and in vivo activation. Using a γ-secretase inhibitor, which blocks Notch signalling through all Notch receptors, we demonstrated that the Notch pathway regulates IL-10 production by CD4+ T cells and IFN-γ and IL-17 production by CD8+ T cells. These results suggest that Notch 1 and 2 are expressed by CD4+ and CD8+ T cells and represent the putative Notch receptors that regulate effector functions and cytokine production by these cells.
Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile Fundacion Ciencia para la Vida, Santiago, Chile.
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D
Sauma
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A
Ramirez
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K
Alvarez
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M
Rosemblatt
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MR
Bono
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051880:Receptors, Notch / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013950:Thymus Gland / Q000276:immunology
D016207:Cytokines; D051880:Receptors, Notch