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Title: Age and CD161 Expression Contribute to Inter-Individual Variation in Interleukin-23 Response in CD8+ Memory Human T Cells
Authors: Shen H. 
Zhang W.
Abraham C.
Cho J.H.
Keywords: CD161 antigen
interleukin 23
interleukin 23 receptor
retinoid related orphan receptor alpha
retinoid related orphan receptor gamma
STAT3 protein
antigen expression
CD4+ T lymphocyte
CD8+ T lymphocyte
controlled study
fluorescence activated cell sorting
gene expression
gene expression profiling
human cell
memory T lymphocyte
natural killer cell
protein expression
protein phosphorylation
real time polymerase chain reaction
Th17 cell
Western blotting
Age Factors
B-Lymphocyte Subsets
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cells, Cultured
Gene Expression
Genetic Variation
Immunologic Memory
Middle Aged
NK Cell Lectin-Like Receptor Subfamily B
Nuclear Receptor Subfamily 1, Group F, Member 3
Receptors, Interleukin
Signal Transduction
STAT3 Transcription Factor
T-Lymphocyte Subsets
Issue Date: 2013
Citation: Shen H., Zhang W., Abraham C., Cho J.H. (2013). Age and CD161 Expression Contribute to Inter-Individual Variation in Interleukin-23 Response in CD8+ Memory Human T Cells. PLoS ONE 8 (3) : e57746. ScholarBank@NUS Repository.
Abstract: The interleukin-23 (IL-23) pathway plays a critical role in the pathogenesis of multiple chronic inflammatory disorders, however, inter-individual variability in IL-23-induced signal transduction in circulating human lymphocytes has not been well-defined. In this study, we observed marked, reproducible inter-individual differences in IL-23 responsiveness (measured by STAT3 phosphorylation) in peripheral blood CD8+CD45RO+ memory T and CD3+CD56+ NKT cells. Age, but not gender, was a significant (Pearson's correlation coefficient, r = -0.37, p = 0.001) source of variability observed in CD8+CD45RO+ memory T cells, with IL-23 responsiveness gradually decreasing with increasing age. Relative to cells from individuals demonstrating low responsiveness to IL-23 stimulation, CD8+CD45RO+ memory T cells from individuals demonstrating high responsiveness to IL-23 stimulation showed increased gene expression for IL-23 receptor (IL-23R), RORC (ROR?t) and CD161 (KLRB1), whereas RORA (ROR?) and STAT3 expression were equivalent. Similar to CD4+ memory T cells, IL-23 responsiveness is confined to the CD161+ subset in CD8+CD45RO+ memory T cells, suggesting a similar CD161+ precursor as has been reported for CD4+ Th17 cells. We observed a very strong positive correlation between IL-23 responsiveness and the fraction of CD161+, CD8+CD45RO+ memory T cells (r = 0.80, p<0.001). Moreover, the fraction of CD161+, CD8+CD45RO+ memory T cells gradually decreases with aging (r = -0.34, p = 0.05). Our data define the inter-individual differences in IL-23 responsiveness in peripheral blood lymphocytes from the general population. Variable expression of CD161, IL-23R and RORC affects IL-23 responsiveness and contributes to the inter-individual susceptibility to IL-23-mediated defenses and inflammatory processes. © 2013 Shen et al.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0057746
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