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Immunology. 2010 Jul;130(3):418-26. doi: 10.1111/j.1365-2567.2009.03244.x. Epub 2010 May 4.

Interleukin-7 promotes the survival of human CD4+ effector/memory T cells by up-regulating Bcl-2 proteins and activating the JAK/STAT signalling pathway.

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1
Centre de Recherche en Rhumatologie/Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and Faculté de Médecine, Université Laval, Québec, PQ, Canada.

Abstract

Interleukin-7 (IL-7) is a crucial cytokine involved in T-cell survival and development but its signalling in human T cells, particularly in effector/memory T cells, is poorly documented. In this study, we found that IL-7 protects human CD4(+) effector/memory T cells from apoptosis induced upon the absence of stimulation and cytokines. We show that IL-7 up-regulates not only Bcl-2 but also Bcl-xL and Mcl-1 as well. Interleukin-7-induced activation of the janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is sufficient for cell survival and up-regulation of Bcl-2 proteins. In contrast to previous studies with naive T cells, we found that IL-7 is a weak activator of the phosphatidylinositol 3 kinase (PI3K)/AKT (also referred as protein kinase B) pathway and IL-7-mediated cell survival occurs independently from the PI3K/AKT pathway as well as from activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Considering the contribution of both IL-7 and CD4(+) effector/memory T cells to the pathogenesis of autoimmune diseases such as rheumatoid arthritis and colitis, our study suggests that IL-7 can contribute to these diseases by promoting cell survival. A further understanding of the mechanisms of IL-7 signalling in effector/memory T cells associated with autoimmune inflammatory diseases may lead to potential new therapeutic avenues.

PMID:
20465565
PMCID:
PMC2913221
DOI:
10.1111/j.1365-2567.2009.03244.x
[Indexed for MEDLINE]
Free PMC Article

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