BJ-3105, a 6-Alkoxypyridin-3-ol Analog, Impairs T Cell Differentiation and Prevents Experimental Autoimmune Encephalomyelitis Disease Progression
- Title
- BJ-3105, a 6-Alkoxypyridin-3-ol Analog, Impairs T Cell Differentiation and Prevents Experimental Autoimmune Encephalomyelitis Disease Progression
- Author
- 남태규
- Keywords
- MULTIPLE-SCLEROSIS; ENCEPHALITOGENIC ANTIGENS; IMMUNE DEVIATION; TH17 CELLS; IN-VIVO; GM-CSF; CYTOKINES; IL-17; PATHOGENESIS; INDUCTION
- Issue Date
- 2017-01
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v. 12, No. 1, Article no. e0168942
- Abstract
- CD4+ T cells are essential in inflammation and autoimmune diseases. Interferon-γ (IFN-γ) secreting T helper (Th1) and IL-17 secreting T helper (Th17) cells are critical for several autoimmune diseases. To assess the inhibitory effect of a given compound on autoimmune disease, we screened many compounds with an in vitro Th differentiation assay. BJ-3105, a 6-alkoxypyridin-3-ol analog, inhibited IFN-γ and IL-17 production from polyclonal CD4+ T cells and ovalbumin (OVA)-specific CD4+ T cells which were activated by T cell receptor (TCR) engagement. BJ-3105 ameliorated the experimental autoimmune encephalomyelitis (EAE) model by reducing Th1 and Th17 generation. Notably, Th cell differentiation was significantly suppressed by BJ-3105 treatment without inhibiting in vitro proliferation of T cells or inducing programmed cell death. Mechanistically, BJ-3105 inhibited the phosphorylation of JAK and its downstream signal transducer and activator of transcription (STAT) that is critical for Th differentiation. These results demonstrated that BJ-3105 inhibits the phosphorylation of STAT in response to cytokine signals and subsequently suppressed the differentiation of Th cell responses.
- URI
- http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168942https://repository.hanyang.ac.kr/handle/20.500.11754/71780
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0168942
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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