title: BJ-3105, a 6-Alkoxypyridin-3-ol Analog, Impairs T Cell Differentiation and Prevents Experimental Autoimmune Encephalomyelitis Disease Progression.
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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Maheshwor
authors.initials: M
authors.lastname: Timilshina
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Youra
authors.initials: Y
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Ishmit
authors.initials: I
authors.lastname: Dahal
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: You
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea.
authors.forename: Tae-Gyu
authors.initials: TG
authors.lastname: Nam
authors.affiliation: Department of Biomedical Laboratory Science, Daekyeung College, Gyeongsan, Republic of Korea.
authors.forename: Keuk-Jun
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Byeong-Seon
authors.initials: BS
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Jae-Hoon
authors.identifier: http://orcid.org/0000-0002-1001-6570
authors.initials: JH
authors.lastname: Chang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C000621990:BJ-3105; D011725:Pyridines; C023666:pyridine