TH-17 cells in rheumatoid arthritis.
TH-17 cells in rheumatoid arthritis.
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DOI:
10.1186/ar2477
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发表时间:
2008
影响因子:
4.9
通讯作者:
Pope RM
中科院分区:
文献类型:
--
作者:
Shahrara S;Huang Q;Mandelin AM 2nd;Pope RM
The aim of this study was to quantify the number of T-helper (TH)-17 cells present in rheumatoid arthritis (RA) synovial fluid (SF) and to determine the level of interleukin (IL)-17 cytokine in RA, osteoarthritis (OA) and normal synovial tissue, as well as to examine SF macrophages for the presence of IL-23, IL-27 and interferon (IFN)-γ. Peripheral blood (PB) mononuclear cells from normal and RA donors and mononuclear cells from RA SF were examined either without stimulation or after pretreatment with IL-23 followed by stimulation with phorbol myristate acetate (PMA) plus ionomycin (P/I). The abundance of TH-17 cells in RA SF was determined by flow cytometry. IL-17 levels were quantified in synovial tissue from RA, OA and normal individuals by ELISA and IL-23 was identified in SFs by ELISA. RA SF and control in vitro differentiated macrophages were either untreated or treated with the toll-like receptor (TLR) 2 ligand peptidoglycan, and then IL-23, IL-27 and IFN-γ mRNA levels were quantified by real-time polymerase chain reaction (RT-PCR). Treatment with P/I alone or combined with IL-23 significantly increased the number of TH-17 cells in normal, RA PB and RA SF. With or without P/I plus IL-23, the percentage of TH-17 cells was higher in RA SF compared with normal and RA PB. IL-17 levels were comparable in OA and normal synovial tissues, and these values were significantly increased in RA synovial tissue. Although IL-17 was readily detected in RA SFs, IL-23 was rarely identified in RA SF. However, IL-23 mRNA was significantly increased in RA SF macrophages compared with control macrophages, with or without TLR2 ligation. IL-27 mRNA was also significantly higher in RA SF compared with control macrophages, but there was no difference in IL-27 levels between RA and control macrophages after TLR2 ligation. IFN-γ mRNA was also detectable in RA SF macrophages but not control macrophages and the increase of IFN-γ mRNA following TLR2 ligation was greater in RA SF macrophages compared with control macrophages. These observations support a role for TH-17 cells in RA. Our observations do not strongly support a role for IL-23 in the generation of TH-17 cells in the RA joint, however, they suggest strategies that enhance IL-27 or IFN-γ might modulate the presence of TH-17 cells in RA.
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影响因子:
30.5
作者:
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者:
Sallusto, Federica
影响因子:
30.5
作者:
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者:
Littman, Dan R.
影响因子:
4
作者:
Kageyama, Yasunori;Ichikawa, Tetsuya;Nagano, Akira
通讯作者:
Nagano, Akira
影响因子:
30.5
作者:
Volpe, Elisabetta;Servant, Nicolas;Soumelis, Vassili
通讯作者:
Soumelis, Vassili
影响因子:
4.9
作者:
Raza K;Falciani F;Curnow SJ;Ross EJ;Lee CY;Akbar AN;Lord JM;Gordon C;Buckley CD;Salmon M
通讯作者:
Salmon M