title: BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis.
abstract: BACKGROUND
  CD4+T cells play an important role in the initiation of an immune response by providing help to other cells. Among the helper T subsets, interferon-γ (IFN-γ)-secreting T helper 1 (Th1) and IL-17-secreting T helper 17 (Th17) cells are indispensable for clearance of intracellular as well as extracellular pathogens. However, Th1 and Th17 cells are also associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases.
  
  
  RESULTS
  In the current study, we found that BJ-1108, a 6-aminopyridin-3-ol analogue, significantly inhibited Th1 and Th17 differentiation in vitro in a concentration-dependent manner, with no effect on proliferation or apoptosis of activated T cells. Moreover, BJ-1108 inhibited differentiation of Th1 and Th17 cells in ovalbumin (OVA)-specific OT II mice. A complete Freund's adjuvant (CFA)/OVA-induced inflammatory model revealed that BJ-1108 can reduce generation of proinflammatory Th1 and Th17 cells. Furthermore, in vivo studies showed that BJ-1108 delayed onset of disease and suppressed experimental autoimmune encephalomyelitis (EAE) disease progression by inhibiting differentiation of Th1 and Th17 cells.
  
  
  CONCLUSIONS
  BJ-1108 treatment ameliorates inflammation and EAE by inhibiting Th1 and Th17 cells differentiation. Our findings suggest that BJ-1108 is a promising novel therapeutic agent for the treatment of inflammation and autoimmune disease.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea.
authors.forename: Youra
authors.initials: Y
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea.
authors.forename: Maheshwor
authors.initials: M
authors.lastname: Timilshina
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do, 15588, Republic of Korea.
authors.forename: Tae-Gyu
authors.initials: TG
authors.lastname: Nam
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea. jeongb@ynu.ac.kr.
authors.forename: Byeong-Seon
authors.initials: BS
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea. jchang@yu.ac.kr.
authors.forename: Jae-Hoon
authors.identifier: http://orcid.org/0000-0002-1001-6570
authors.initials: JH
authors.lastname: Chang
mesh_terms: D000631:Aminopyridines / Q000276:immunology / Q000494:pharmacology*; D000814:Aniline Compounds / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000276:immunology; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D000631:Aminopyridines; D000814:Aniline Compounds; C000609005:BJ-1108
keywords: BJ-1108; Differentiation; EAE; Th1/Th17 cell