Study on ratio imbalance of peripheral blood Th17/Treg cells in patients with rheumatoid arthritis
To observe the relationship between balance of peripheral blood Th17 cells and Foxp3(+) CD4(+) CD25(+) regulatory T (Treg) cells in patients with rheumatoid arthritis (RA), and to clarify the role the ratio imbalance of peripheral blood Th17/Treg cells playing in pathogenesis of RA.
The ratio of peripheral blood Th17 cells and Foxp3(+) CD4(+) CD25(+) Treg cells in RA patients and healthy subjects were determined by flow cytometry (FCM).
Compared with healthy controls, the ratio of both CD3(+) CD4(+) T cells and Th17 cells in RA patients increased significantly (P<0.05), while the percentage of Foxp3(+) CD4(+) CD25(+) Treg cells was markedly lower (P<0.05). With the development of RA activity, the ratio of Th17 cells increased (P<0.05), and the ratio of Foxp3(+) CD4(+) CD25(+) Treg cells decreased (P>0.05).
The disorder of peripheral blood T lymphocyte subsets in RA patients characterized by increased CD4(+) T cells. The imbalance between Th17 cells and Foxp3(+) CD4(+) CD25(+) Treg cells resulted from increased ratio of Th17 cells and decreased ratio of Foxp3(+) CD4(+) CD25(+) Treg cells may play a critical role in RA progression.
Available from: Farhad Jadidi-Niaragh
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ABSTRACT: Identifying the regulatory T cells (Tregs) and Th17 cells led to breaking the dichotomy of Th1/Th2 cells axis in immune responses involved in several autoimmune diseases. It is now well known that Tregs and Th17 cells are main orchestra leaders in pathogenesis symphony of autoimmunity. While Tregs are protective cells in autoimmune diseases, Th17 cells enhance the progression of autoimmune responses through induction of various pro-inflammatory reactions. It seems that the progression of autoimmunity may be associated with increase in Th17 and decrease in Treg levels, so that skewed balance between Tregs and Th17 toward Th17 is a phenomenon, which could be observed during progression of several autoimmune diseases. Although it is suggested that expansion and transfer of Tregs can be a new therapeutic target for autoimmune diseases, however, recent data about the phenotype conversion of Tregs into Th17 cells obligate us to more investigation on this approaching. Thus, identifying the new factors that induce stable phenotype in Tregs and prevent their phenotype conversion into Th17 cells as well as targeting the factor, which can modulate their balance, might be recommended as a new promising therapeutic method for autoimmune therapy. In this review, we try to clarify the factors, which can affect on this balance in various autoimmune diseases, as new targets in treatment of these diseases.
Immunopharmacology and Immunotoxicology 02/2012; 34(5):727-39. DOI:10.3109/08923973.2011.619987 · 1.20 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the synovial joints, joint malformations, and disability. The continuous use of conventional anti-inflammatory drugs is associated with severe adverse effects. Grape seed proanthocyanidin extract (GSPE) is considered to have protective effects against several diseases. In this study based on the mouse adjuvant-induced-arthritis (AIA) model, we examined the effects of GSPE on the key mediators of arthritic inflammation, namely T cell subsets, glucocorticoid-induced tumour necrosis factor receptor (GITR) expressing cells, CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, Th17 cells, Th1/Th2 cytokines, and inflammatory mediator gene expression. We treated BALB/c mice with 25, 50, or 100mg/kg GSPE or saline daily (14days) per orally (p.o.) at the onset of AIA. At the peak phase of AIA (day 14), the heparinised whole blood and ankle joints of all groups were collected and tested. GSPE-treated mice showed a substantial reduction in the levels of T cell subsets, GITR-expressing cells, and Th1 cytokines as well as the inflammatory mediators (MCP-1, MIP-2, and ICAM-1) that induce them compared with the vehicle-treated (saline) and arthritic mice. However, GSPE significantly upregulated the number of Tregs and Th2 cytokine producing cell number or it also induced Th17/Treg rebalance and orchestrated various pro-inflammatory and anti-inflammatory cytokines and the gene expression of their mediators that mediate cellular infiltration into the joints. This might, contribute to its anti-arthritic activity. Our results suggest that p.o. treatment with GSPE attenuated AIA in mice might offer a promising alternative/adjunct treatment for RA.
International immunopharmacology 06/2013; 17(1). DOI:10.1016/j.intimp.2013.05.026 · 2.47 Impact Factor
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ABSTRACT: Rheumatoid arthritis is characterized by type 17 helper T cell (Th17)/regulatory T cell (Treg) imbalance. The objective of this article is to study whether insufficient apoptosis contributes to the imbalance of Th17/Treg in rheumatoid arthritis.
Twenty-one rheumatoid arthritis patients and eight healthy volunteers were involved in this study. The percentage of CD4(+) interleukin (IL)-17(+) T cells and CD4(+) transcription factor-forkhead box protein 3 (Foxp3)(+) T cells were measured by flow cytometry, and active caspase-3 labeling was used to detect early apoptosis. The number of T cell subtypes in peripheral blood between the two groups was compared, as well as the apoptotic ratio.
Neither the number of Th17 nor Treg cells was significantly different between rheumatoid arthritis patients and healthy controls. However, the number of regulatory T cells positively correlated with erythrocyte sedimentation rate, Disease Activity Score of 28 joints and rheumatoid factor. For the apoptosis of T cell subtypes, the percentage of apoptotic Th17 cells was higher in peripheral blood of rheumatoid arthritis patients compared to controls. Furthermore, peripheral Th17 cells were more sensitive to apoptosis than Treg cells, but there was no difference between rheumatoid arthritis patients and controls.
It seemed that there was no relationship between the number and apoptosis ratio of peripheral Th17/Treg cells. But the number of Treg cells positively correlated with disease activity. Furthermore, Th17 cells are more sensitive to apoptosis after freezing, especially in RA patients. This serendipitous finding may provide new areas for the further study of these two cell populations.
International Journal of Rheumatic Diseases 10/2013; DOI:10.1111/1756-185X.12211 · 1.47 Impact Factor
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