scholarly journals Soufeng Sanjie Formula Alleviates Collagen-induced Arthritis in Mice by Inhibiting Th17 Cell Differentiation

2021 ◽  
Author(s):  
Di Hua ◽  
Jie Yang ◽  
Qinghai Meng ◽  
Yuanyuan Ling ◽  
Qin Wei ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Lymph Nodes ◽  
Inflammatory Cytokines ◽  
Th17 Cell ◽  
Soybean Seed ◽  
Collagen Induced Arthritis ◽  
Th17 Cell Differentiation ◽  
Spleen And Lymph Nodes ◽  
Seed Coats

Abstract Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), and is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remain unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice.Methods: For in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/d) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 d, degree of ankle joint inflammatory infiltration and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in Th17 polarization.Results: SF decreased the arthritis score, ameliorated paw swelling, and reduced synovial hyperplasia in the joints of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG and inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 in the sera of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, and Il-17A under Th17 polarization conditions.Conclusions: Our results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.

scholarly journals Soufeng sanjie formula alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Di Hua ◽  
Jie Yang ◽  
Qinghai Meng ◽  
Yuanyuan Ling ◽  
Qin Wei ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Lymph Nodes ◽  
Inflammatory Cytokines ◽  
Th17 Cell ◽  
Collagen Induced Arthritis ◽  
Expression Levels ◽  
Th17 Cell Differentiation ◽  
Spleen And Lymph Nodes ◽  
Seed Coats

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remains unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice. Methods For in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/day) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 days, degree of ankle joint destruction and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Moreover, the expression levels of retinoic acid receptor-related orphan nuclear receptor (ROR) γt and phosphorylated STAT3 (pSTAT3, Tyr705) in the spleen were detected by immunohistochemistry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in CD4+ T cells under Th17 polarization conditions. Results SF decreased the arthritis score, ameliorated paw swelling, and reduced cartilage loss in the joint of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG in sera of CIA mice. SF decreased the levels of inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 both in the sera and the joint of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. SF also reduced the expression levels of ROR γt and pSTAT3 (Tyr705) in the spleen of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, IL-17A, and pSTAT3 (Tyr705) under Th17 polarization conditions. Conclusions Our results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.

A1.7 The regulation of human in vitro TH17 cell differentiation

2015 ◽  
Vol 74 (Suppl 1) ◽  
pp. A3.1-A3
Author(s):  
E Baricza ◽  
E Lajkó ◽  
L Kőhidai ◽  
B Molnár-Érsek ◽  
N Marton ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Th17 Cell ◽  
Th17 Cell Differentiation

scholarly journals Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes

Cell Reports ◽  
2021 ◽  
Vol 36 (12) ◽  
pp. 109766
Author(s):  
Teruyuki Sano ◽  
Takahiro Kageyama ◽  
Victoria Fang ◽  
Ranit Kedmi ◽  
Carlos Serafin Martinez ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Lymph Nodes ◽  
Intestinal Microbiota ◽  
Th17 Cell ◽  
Th17 Cell Differentiation ◽  
Draining Lymph Nodes

scholarly journals PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation

2020 ◽  
Vol 217 (10) ◽  
Author(s):  
Luis Eduardo Alves Damasceno ◽  
Douglas Silva Prado ◽  
Flavio Protasio Veras ◽  
Miriam M. Fonseca ◽  
Juliana E. Toller-Kawahisa ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Glycolytic Enzyme ◽  
Metabolic Reprogramming ◽  
Fine Tuning ◽  
Autoimmune Inflammation ◽  
Th17 Cell Differentiation ◽  
Key Factor

Th17 cell differentiation and pathogenicity depend on metabolic reprogramming inducing shifts toward glycolysis. Here, we show that the pyruvate kinase M2 (PKM2), a glycolytic enzyme required for cancer cell proliferation and tumor progression, is a key factor mediating Th17 cell differentiation and autoimmune inflammation. We found that PKM2 is highly expressed throughout the differentiation of Th17 cells in vitro and during experimental autoimmune encephalomyelitis (EAE) development. Strikingly, PKM2 is not required for the metabolic reprogramming and proliferative capacity of Th17 cells. However, T cell–specific PKM2 deletion impairs Th17 cell differentiation and ameliorates symptoms of EAE by decreasing Th17 cell–mediated inflammation and demyelination. Mechanistically, PKM2 translocates into the nucleus and interacts with STAT3, enhancing its activation and thereby increasing Th17 cell differentiation. Thus, PKM2 acts as a critical nonmetabolic regulator that fine-tunes Th17 cell differentiation and function in autoimmune-mediated inflammation.

scholarly journals CD147 Is Essential for the Development of Psoriasis via the Induction of Th17 Cell Differentiation

2021 ◽  
Vol 23 (1) ◽  
pp. 177
Author(s):  
Aoi Okubo ◽  
Youhei Uchida ◽  
Yuko Higashi ◽  
Takuya Sato ◽  
Youichi Ogawa ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Transmembrane Protein ◽  
Immunoglobulin Superfamily ◽  
Monocarboxylate Transporters ◽  
Th17 Cell Differentiation

Th17 cells play an important role in psoriasis. The differentiation of naïve CD4+ T cells into Th17 cells depends on glycolysis as the energy source. CD147/basigin, an integral transmembrane protein belonging to the immunoglobulin superfamily, regulates glycolysis in association with monocarboxylate transporters (MCTs)-1 and -4 in cancer cells and T cells. We examined whether CD147/basigin is involved in the pathogenesis of psoriasis in humans and psoriasis-model mice. The serum level of CD147 was increased in patients with psoriasis, and the expression of CD147 and MCT-1 was elevated in their dermal CD4+ RORγt+ T cells. In vitro, the potential of naïve CD4+ T cells to differentiate into Th17 cells was abrogated in CD147−/− T cells. Imiquimod (IMQ)-induced psoriatic dermatitis was significantly milder in CD147−/− mice and bone marrow chimeric mice lacking CD147 in the hematopoietic cells of myeloid lineage. These findings demonstrate that CD147 is essential for the development of psoriasis via the induction of Th17 cell differentiation.

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