Human High sensitive Interleukin 17 ELISA Kit

Objectives: Indirubin (IR) is a bisindole compound extracted from the leaves of Chinese herb Indigo Naturalis. Indigo Naturalis has been widely used in traditional Chinese medicine to treat inflammatory and autoimmune diseases. Psoriasis is a chronic immune-mediated inflammatory skin disease in which gamma delta T cells play an important role. This study aims to determine the immunoregulatory effects and the underlying mechanisms of Indirubin in psoriasis-related inflammatory responses. Methods: BALB/c mice with imiquimod (IMQ)-induced psoriasis-like dermatitis were treated with saline (Model), 1 mg/kg methotrexate (MTX) that serves as a positive control, or 12.5, 25 and 50 mg/kg Indirubin(IR) intragastrically. Keratinocytes proliferation, inflammatory cells infiltration, the expression of inflammatory cytokines and Jak/Stat pathway-related proteins in the skin lesion were examined. The abundance of gamma delta T cells in lymph nodes and spleen was determined by flow cytometry. The IL-17 expression and secretion, and the activation of Jak3/Stat3 pathways in in vitro cultured gamma delta T cell were tested. Results: Indirubin ameliorated keratinocyte proliferation, reduced the infiltration of CD3(+) T cells, IL-17 A-producing gamma delta T cells, and CD11b(+) neutrophils, inhibited the mRNA expression of Il1, Il6, Il23,Il17a and Il22, and the protein expression of Jak/Stat pathway-related molecules in the skin lesion. Indirubin also reduced the abundance of gamma delta T cell and CCR6(+) gamma delta T cells (the major IL-17 A producer) in spleen and lymph nodes. In cultured gamma delta T cells, Indirubin inhibited the mRNA expression of Il17a and Ifng, and the secretion of IL-17 A, while suppressed the activation of Jak3/Stat3 pathways. Conclusion: Indirubin alleviates IMQ-induced psoriasis-like dermatitis mainly through reducing the inflammatory responses mediated by IL-17 A-producing gamma delta T cells involving Jak3/Stat3 activation. Our results highlighted the novel mechanisms by which Indirubin ameliorates psoriasis-related inflammatory responses, supporting its therapeutic potential.

Phosphatase PP2A expression levels are positively correlated to the clinical severity of systemic lupus erythematosus (SLE) and IL17A cytokine overproduction, indicating a potential role of PP2A in controlling T(H)17 differentiation and inflammation. By generating a mouse strain with ablation of the catalytic subunit alpha of PP2A in peripheral mature T cells (PP2A cKO), we demonstrate that the PP2A complex is essential for T(H)17 differentiation. These PP2A cKO mice had reduced T(H)17 cell numbers and less severe disease in an experimental autoimmune encephalomyelitis (EAE) model. PP2A deficiency also ablated C-terminal phosphorylation of SMAD2 but increased C-terminal phosphorylation of SMAD3. By regulating the activity of ROR gamma t via binding, the changes in the phosphorylation status of these R-SMADs reduced Il17a gene transcription. Finally, PP2A inhibitors showed similar effects on T(H)17 cells as were observed in PP2A cKO mice, i.e., decreased T(H)17 differentiation and relative protection of mice from EAE. Taken together, these data demonstrate that phosphatase PP2A is essential for T(H)17 differentiation and that inhibition of PP2A could be a possible therapeutic approach to controlling T(H)17-driven autoimmune diseases.