Thal treatment: (a) reduced skin, and pulmonary tissue fibrosis, inflammation score, and hydroxyproline content (P < .001) in BLM-induced SSc mice; (b) reduced the percentages of Th17 cells and associated interleukin (IL)-17A expression (both P < .05) but increased the percentages of Treg cells and its transcription factor Foxp3 expression (both P < .05); (c) correlation analysis found positive correlations between Th17/Treg ratio, the inflammatory score of the skin and pulmonary tissues, hydroxyproline content, and type I collagen messenger RNA expression (r = .8546, .8656, .6902, .6807, .8118, and .8424, respectively, P < .01); (d) Thal inhibited TGF-β1 expression and Smad3 phosphorylation (both P < .05); (e) TGF-β1 was positively correlated with the IL-17A and Th17/Treg ratio (r = .5856, P = .005; r = .6684, P = .0107, respectively).
Thal treatment: (a) reduced skin, and pulmonary tissue fibrosis, inflammation score, and hydroxyproline content (P < .001) in BLM-induced SSc mice; (b) reduced the percentages of Th17 cells and associated interleukin (IL)-17A expression (both P < .05) but increased the percentages of Treg cells and its transcription factor Foxp3 expression (both P < .05); (c) correlation analysis found positive correlations between Th17/Treg ratio, the inflammatory score of the skin and pulmonary tissues, hydroxyproline content, and type I collagen messenger RNA expression (r = .8546, .8656, .6902, .6807, .8118, and .8424, respectively, P < .01); (d) Thal inhibited TGF-β1 expression and Smad3 phosphorylation (both P < .05); (e) TGF-β1 was positively correlated with the IL-17A and Th17/Treg ratio (r = .5856, P = .005; r = .6684, P = .0107, respectively).
Thal can effectively prevent skin and pulmonary tissue fibrosis in a mouse model of SSc through the TGF-β1/Smad3 signaling pathway and can rectify the distortion of the Th17/Treg balance in SSc by potentially regulating Th17 and Treg cell production, as well as their related factors expression.
Thal treatment: (a) reduced skin, and pulmonary tissue fibrosis, inflammation score, and hydroxyproline content (P < .001) in BLM-induced SSc mice; (b) reduced the percentages of Th17 cells and associated interleukin (IL)-17A expression (both P < .05) but increased the percentages of Treg cells and its transcription factor Foxp3 expression (both P < .05); (c) correlation analysis found positive correlations between Th17/Treg ratio, the inflammatory score of the skin and pulmonary tissues, hydroxyproline content, and type I collagen messenger RNA expression (r = .8546, .8656, .6902, .6807, .8118, and .8424, respectively, P < .01); (d) Thal inhibited TGF-β1 expression and Smad3 phosphorylation (both P < .05); (e) TGF-β1 was positively correlated with the IL-17A and Th17/Treg ratio (r = .5856, P = .005; r = .6684, P = .0107, respectively).
Forty female BALB/c mice were randomly divided into a normal control (NC) group, SSc group (bleomycin [BLM]-induced experimental SSc), BLM + Thal (10 mg/kg/day) group, BLM + Thal (20) group, and BLM + Thal (30) group.Thal was administered a day after BLM.
Our meta-analysis showed that the FAS-670 A/G polymorphism was associated with the risk of autoimmune diseases (GG vs. GA: OR=1.079, 95% CI=1.004-1.160, P=0.038), especially in Caucasians (GG vs. GA: OR=1.12, 95% CI=1.03-1.23, P=0.012), Asians (G vs. A: OR=0.89, 95% CI=0.83-0.96, P=0.002), systemic lupus erythematosus (SLE) (G vs. A: OR=0.85, 95% CI=0.77-0.94, P=0.001), multiple sclerosis (MS) (GG+GA vs. AA: OR=0.83, 95% CI=0.70-0.99, P=0.043), systemic sclerosis (SSc) (GG vs. GA: OR=1.20, 95% CI=1.07-1.36, P=0.003) and Hashimoto's thyroiditis (HT) (G vs. A: OR=1.45, 95% CI=1.10-1.90, P=0.008); the FAS-1377 G/A polymorphism was associated with the risk of autoimmune diseases (A vs. G: OR=1.11, 95% CI=1.03-1.20, P=0.008), especially in Asians (A vs. G: OR=1.15, 95% CI=1.05-1.25, P=0.002) and high quality studies (A vs. G: OR=1.14, 95% CI=1.05-1.24, P=0.002).
Our meta-analysis showed that the FAS -670 A/G polymorphism was associated with the risk of autoimmune diseases (GG vs. GA: OR=1.079, 95% CI=1.004-1.160, P=0.038), especially in Caucasians (GG vs. GA: OR=1.12, 95% CI=1.03-1.23, P=0.012), Asians (G vs. A: OR=0.89, 95% CI=0.83-0.96, P=0.002), systemic lupus erythematosus (SLE) (G vs. A: OR=0.85, 95% CI=0.77-0.94, P=0.001), multiple sclerosis (MS) (GG+GA vs. AA: OR=0.83, 95% CI=0.70-0.99, P=0.043), systemic sclerosis (SSc) (GG vs. GA: OR=1.20, 95% CI=1.07-1.36, P=0.003) and Hashimoto's thyroiditis (HT) (G vs. A: OR=1.45, 95% CI=1.10-1.90, P=0.008); the FAS -1377 G/A polymorphism was associated with the risk of autoimmune diseases (A vs. G: OR=1.11, 95% CI=1.03-1.20, P=0.008), especially in Asians (A vs. G: OR=1.15, 95% CI=1.05-1.25, P=0.002) and high quality studies (A vs. G: OR=1.14, 95% CI=1.05-1.24, P=0.002).
Activation of mTOR has been implicated in a number of chronic inflammatory diseases, especially rheumatic diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), sjögren syndrome (SS) and seronegative spondyloarthropathy (SpA).
<b>Objectives:</b> The usage of oral therapies, endothelin receptor antagonists (ERA), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogues has resulted in improved outcomes in patients with pulmonary arterial hypertension related to systemic sclerosis (SSc-PAH).
Over the observed time span (7.6 (1.0-19.5) years), 18.3% (n = 24) of patients had continuously elevated CRP levels (inflammatory SSc), whereas in 29% (n = 38), CRP levels were always in the normal range.
Discrimination of CD4+ T cells that lack CCR7 expression revealed that CCR7- CD4+ memory T cells and effectors are producers of intracellular TNFα, IL-13 and IL-4, particularly in dcSSc.
Discrimination of CD4+ T cells that lack CCR7 expression revealed that CCR7- CD4+ memory T cells and effectors are producers of intracellular TNFα, IL-13 and IL-4, particularly in dcSSc.
In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages (MHEs) and microthromboses (MTs), observed in nailfold videocapillaroscopy was a good indicator of the steady state level of disease activity (DA) in patients with systemic sclerosis (SSc) when the European Scleroderma Study Group (EScSG) index was considered the gold standard.
In conclusion, TH17 cells expressing CD146 could represent a new component of the adaptive immune response, opening the way for the generation of new tools for the management of SSc.