title: CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis.
abstract: There is increasing interest in the role of T follicular helper (Tfh) cells in autoimmunity from the perspective of both their role in breach of tolerance and their effects on the natural history of disease progression. Indeed, the critical role of Tfh cells in autoimmunity is further highlighted based on their location in the germinal center (GC), a pathogenic hot spot for development of autoreactivity. To address the role of Tfh cells in primary biliary cirrhosis (PBC), we comprehensively evaluated the immunobiology of CXCR5(+) CD4(+) Tfh cells in 69 patients with PBC, including a nested subgroup of 16 autoimmune hepatitis (AIH) and 20 healthy controls (HC), followed for 1 year. We report herein several key observations. First, there was an increased frequency of circulating Tfh cells in patients with PBC compared to AIH (P < 0.05) and HC (P < 0.01). Second, the function of circulating Tfh cells from PBC patients, including interleukin (IL)-21 production (P < 0.05), the ability to promote B-cell maturation, and autoantibody production, were greater than HC. Third, the frequency of these cells was significantly decreased in ursodeoxycholic acid (UDCA) responders compared to UDCA-treated nonresponders, in both cross-sectional (P = 0.023) and longitudinal studies (P = 0.036), respectively. Indeed, similar increases of Tfh cells were noted in liver and spleen.
  
  
  CONCLUSIONS
  These results significantly extend our understanding of lymphoid subpopulations in PBC and their relative role in disease expression. Our data also provide a novel biomarker for evaluation of the effectiveness of new therapeutic approaches.
authors.affiliation: Research Center for Biological Therapy, Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yiqiong
authors.initials: Y
authors.lastname: Jia
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Zou
authors.forename: Jinbiao
authors.initials: J
authors.lastname: Ding
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.forename: Yanling
authors.initials: Y
authors.lastname: Sun
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Sa
authors.initials: S
authors.lastname: Lv
authors.forename: Liming
authors.initials: L
authors.lastname: Chen
authors.forename: Baosen
authors.initials: B
authors.lastname: Li
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000502:physiology; D016022:Case-Control Studies; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054380:Receptors, CXCR5 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: C095085:CXCR5 protein, human; D002756:Cholagogues and Choleretics; D007378:Interleukins; D054380:Receptors, CXCR5; D014580:Ursodeoxycholic Acid; D000098546:Interleukin-21