CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis

Lifeng Wang, Ying Sun, Zheng Zhang, Yiqiong Jia, Zhengsheng Zou, Jinbiao Ding, Yuanyuan Li, Xiangsheng Xu, Lei Jin, Tao Yang, Zhiwei Li, Yanling Sun, Ji yuan Zhang, Sa Lv, Liming Chen, Baosen Li, M. Eric Gershwin, Fu Sheng Wang

Research output: Contribution to journalArticle

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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. 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.

Original languageEnglish (US)
Pages (from-to)627-638
Number of pages12
JournalHepatology
Volume61
Issue number2
DOIs
StatePublished - Feb 1 2015

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Biliary Liver Cirrhosis
Helper-Inducer T-Lymphocytes
Ursodeoxycholic Acid
Autoimmune Hepatitis
Autoimmunity
Germinal Center
Autoantibodies
Longitudinal Studies
Disease Progression
B-Lymphocytes
Spleen
Biomarkers
Liver

ASJC Scopus subject areas

  • Hepatology

Cite this

Wang, L., Sun, Y., Zhang, Z., Jia, Y., Zou, Z., Ding, J., ... Wang, F. S. (2015). CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis. Hepatology, 61(2), 627-638. https://doi.org/10.1002/hep.27306

CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis. / Wang, Lifeng; Sun, Ying; Zhang, Zheng; Jia, Yiqiong; Zou, Zhengsheng; Ding, Jinbiao; Li, Yuanyuan; Xu, Xiangsheng; Jin, Lei; Yang, Tao; Li, Zhiwei; Sun, Yanling; Zhang, Ji yuan; Lv, Sa; Chen, Liming; Li, Baosen; Gershwin, M. Eric; Wang, Fu Sheng.

In: Hepatology, Vol. 61, No. 2, 01.02.2015, p. 627-638.

Research output: Contribution to journalArticle

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, JY, Lv, S, Chen, L, Li, B, Gershwin, ME & Wang, FS 2015, 'CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis', Hepatology, vol. 61, no. 2, pp. 627-638. https://doi.org/10.1002/hep.27306
Wang, Lifeng ; Sun, Ying ; Zhang, Zheng ; Jia, Yiqiong ; Zou, Zhengsheng ; Ding, Jinbiao ; Li, Yuanyuan ; Xu, Xiangsheng ; Jin, Lei ; Yang, Tao ; Li, Zhiwei ; Sun, Yanling ; Zhang, Ji yuan ; Lv, Sa ; Chen, Liming ; Li, Baosen ; Gershwin, M. Eric ; Wang, Fu Sheng. / CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis. In: Hepatology. 2015 ; Vol. 61, No. 2. pp. 627-638.
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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. 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.",
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AU - Ding, Jinbiao

AU - Li, Yuanyuan

AU - Xu, Xiangsheng

AU - Jin, Lei

AU - Yang, Tao

AU - Li, Zhiwei

AU - Sun, Yanling

AU - Zhang, Ji yuan

AU - Lv, Sa

AU - Chen, Liming

AU - Li, Baosen

AU - Gershwin, M. Eric

AU - Wang, Fu Sheng

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N2 - 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.

AB - 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.

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