These authors contributed equally to this work.
Autoimmune, Cholestatic and Biliary Disease
CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis
Article first published online: 5 JAN 2015
© 2014 by the American Association for the Study of Liver Diseases
Volume 61, Issue 2, pages 627–638, February 2015
How to Cite
Wang, L., Sun, Y., Zhang, Z., Jia, Y., Zou, Z., Ding, J., Li, Y., Xu, X., Jin, L., Yang, T., Li, Z., Sun, Y., Zhang, J.-y., Lv, S., Chen, L., Li, B., Gershwin, M. E. and Wang, F.-S. (2015), CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis. Hepatology, 61: 627–638. doi: 10.1002/hep.27306
Potential conflict of interest: Nothing to report.
Supported by the National Natural Science Foundation of China, grant 81101589; National Institutes of Health grant DK39588; National Grand Program on Key Infectious Disease grants 2012ZX10001006-003-003, 2013ZX10001002-001-002; Beijing Municipal & Technology Commission grant Z131100004013041.
See Editorial on Page 424
- Issue published online: 20 JAN 2015
- Article first published online: 5 JAN 2015
- Accepted manuscript online: 12 JUL 2014 06:31AM EST
- Manuscript Accepted: 7 JUL 2014
- Manuscript Received: 10 FEB 2014
- National Natural Science Foundation of China . Grant Number: 81101589
- National Institutes of Health . Grant Number: DK39588
- National Grand Program on Key Infectious Disease . Grant Number: 2012ZX10001006-003-003, 2013ZX10001002-001-002
- Beijing Municipal & Technology Commission . Grant Number: Z131100004013041
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. Conclusion: 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. (Hepatology 2015;61:627-638)