Anti-STAT4 monoclonal antibody, clone 2H0

Psoriasis is an immune-mediated dermatosis characterized by T-lymphocyte-mediated epidermal hyperplasia, for which there are currently no effective clinical treatments. 'Psoriasis 1' is a Chinese herbal medicine formulation that has been recently used extensively in China for treating patients with psoriasis. However, the molecular mechanism of action of this potent formulation has not yet been fully elucidated. In the present study, the effects of 'Psoriasis 1' on T ymphocytes in patients with psoriasis were investigated and the underlying molecular mechanism was discussed. Blood samples were collected from 40 patients with psoriasis. ELISA was employed to assess the levels of tumour necrosis factor-alpha, interferon-gamma, interleukin (IL)-2, IL-6, transforming growth factor-beta, IL-4, IL-12, IL-23 and vitamin D (VD). Western blot and quantitative PCR analyses were used to investigate the expression levels of VD receptor (VDR) and signal transducer and activator of transcription (STAT)4 in T lymphocytes. 'Psoriasis 1' was observed to significantly increase CD4(+) T cells. It also notably upregulated the mRNA and protein expression of VDR, and downregulated the mRNA and protein expression of STAT4. Moreover, the suppression of VDR was found to aggravate the inflammatory response, which was reversed by 'Psoriasis 1.' Thus, this formulation reportedly decreased the inflammation mediated by T lymphocytes in patients with psoriasis through inhibiting VDR-mediated STAT4 inactivation.

Purpose: The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. Methods: Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. Results: In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-gamma t (ROR gamma t) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed ROR gamma t and Tbet and produced interferon-gamma (IFN-gamma). Increased IFN-gamma-producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-gamma-producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3(+) Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. Conclusions: Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.