title: JAK1-STAT3 blockade by JAK inhibitor SHR0302 attenuates inflammatory responses of adjuvant-induced arthritis rats and decreases Th17 and total B cells.
abstract: OBJECTIVE
  To investigate the effects of JAK inhibitor (SHR0302) on adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Th17, Treg, total B cells and memory B cells.
  
  
  METHODS
  Animals were divided randomly into normal control, AA, SHR0302 (0.3,1.0, 3.0mg/kg) and MTX. The effects of SHR0302 on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen. We examined the proliferation of T, B and FLS. Th17, Treg, total B and memory B cell proportion was measured by flow cytometry. Cytokines TNF-α, IL-1β, IL-10, IL-17 and antibody IgG1, IgG2a levels in serum were measured by Elisa. The expression of p-JAK1 and p-STAT3 was measured by western blot.
  
  
  RESULTS
  SHR0302 suppressed the severity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats. SHR0302 can inhibit the proliferation of T, B and FLS, and down-regulated cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Th17 and total B, and inhibited JAK1-STAT3 phosphorylation. There was no significant effect on Treg function and memory B cell proportion.
  
  
  CONCLUSIONS
  SHR0302 may attenuate the severity of AA rats, partially through reducing Th17 function and total B cell proportion by inhibiting JAK1-STAT3 phosphorylation.
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Huaxun
authors.initials: H
authors.lastname: Wu
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Shangxue
authors.initials: S
authors.lastname: Yan
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Xuexia
authors.initials: X
authors.lastname: Luo
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Jia
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Dai
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Aiwu
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China.
authors.forename: LingLing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of clinical pharmacology of Anhui medical university, 81, meishan road, 230032 Hefei, China; Key laboratory of anti-inflammatory and immune medicine, ministry of Education, 230032 Hefei, China; Anhui collaborative innovation center of anti-inflammatory and immune medicine, 230032 Hefei, China. Electronic address: wwei@ahmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D013464:Sulfuric Acids / Q000494:pharmacology*; D000070918:Synoviocytes / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; D013464:Sulfuric Acids; D053613:Janus Kinase 1; C000615713:ivarmacitinib
keywords: Adjuvant-induced arthritis; JAK inhibitor; Memory B cells; STAT3; Th17; Treg