Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells.
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, reproduci...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3585933?pdf=render |
| _version_ | 1819105993819160576 |
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| author | Hui Shen Wei Zhang Clara Abraham Judy H Cho |
| author_facet | Hui Shen Wei Zhang Clara Abraham Judy H Cho |
| author_sort | Hui Shen |
| collection | DOAJ |
| description | 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 (RORγt) and CD161 (KLRB1), whereas RORA (RORα) 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. |
| first_indexed | 2024-12-22T02:31:05Z |
| format | Article |
| id | doaj.art-828446567be94ec8ad09b61d35351d68 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T02:31:05Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-828446567be94ec8ad09b61d35351d682022-12-21T18:41:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5774610.1371/journal.pone.0057746Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells.Hui ShenWei ZhangClara AbrahamJudy H ChoThe 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 (RORγt) and CD161 (KLRB1), whereas RORA (RORα) 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.http://europepmc.org/articles/PMC3585933?pdf=render |
| spellingShingle | Hui Shen Wei Zhang Clara Abraham Judy H Cho Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells. PLoS ONE |
| title | Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells. |
| title_full | Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells. |
| title_fullStr | Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells. |
| title_full_unstemmed | Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells. |
| title_short | Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells. |
| title_sort | age and cd161 expression contribute to inter individual variation in interleukin 23 response in cd8 memory human t cells |
| url | http://europepmc.org/articles/PMC3585933?pdf=render |
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