Interleukin-17A-Induced Epithelial-Mesenchymal Transition of Human Intrahepatic Biliary Epithelial Cells: Implications for Primary Biliary Cirrhosis
Open accessAbstract
Primary biliary cirrhosis (PBC) is an autoimmune chronic liver disease with worldwide increasing morbidity. However, the etiology of PBC is still unclear. Recently, the epithelial-mesenchymal transition (EMT) and interleukin-17A (IL-17A), a pro-inflammatory cytokine, were proposed to be involved in the pathogenesis of PBC. Therefore, in this study, we aimed to clarify the roles of IL-17A and/or EMT in the onset of PBC. The results showed that the median serum IL-17A level was significantly higher in 29 PBC patients (average course of 40.69 months) than that of 11 healthy controls. The intrahepatic biliary epithelial cells (IBECs), the major target of destruction in PBC, underwent EMT in PBC patients. The immunohistochemical analysis revealed that the protein levels of IL-17A receptor were increased in IBECs and the IL-17A protein was accumulated around the IBECs in the PBC patients. These results imply that the IL-17A-mediated signaling and EMT of intrahepatic biliary epithelial cells (IBEC-EMT) are key pathogenic processes of PBC. To study the association between IL-17A and IBECs-EMT, we then examined if IL-17A induced EMT using a human cell line of IBECs (HIBECs). After the treatment with IL-17A for 48 h, HIBECs changed into bipolar cells with a fibroblastic morphology. Additionally, the results of real-time PCR and Western blot analyses demonstrated that IL-17A up-regulated the expression of a mesenchymal marker vimentin and down-regulated the expression of an epithelial marker E-cadherin in HIBECs in the dose- and time-dependent manners. These results suggest that IL-17A may play an important role in the IBECs-EMT.
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BECs in PBC have a proinflammatory and profibrotic phenotype.
“and have also a proinflammatory and profibrotic phenotype(256).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [256]
The Discussion reports that biliary epithelial cells in early-stage PBC undergo epithelial–mesenchymal transition, and the Introduction links that transition to fibrosis. But the paper attributes pro-inflammatory effects to IL-17A around the cells; it does not establish that the cells themselves have a proinflammatory and profibrotic phenotype. Page numbers are unavailable in our copy. (LLM, conf=0.85)
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Cites
Kaplan, M. M. (1987) · New England Journal of Medicine · doi:10.1056/nejm198702263160907 · Cited by 2,015 · see citing works
Schwab, M. (2011) · Springer eBooks · doi:10.1007/978-3-642-16483-5_4730 · Cited by 1,241 · see citing works
Kaplan, M. M., & Gershwin, M. E. (2005) · New England Journal of Medicine · doi:10.1056/nejmra043898 · Cited by 1,144 · see citing works
Lindor, K. D., Gershwin, E. M., Poupon, R., Kaplan, M., Bergasa, N. V., & Heathcote, J. E. (2009) · Hepatology · doi:10.1002/hep.22906 · Cited by 1,099 · see citing works
(2015) · Elsevier eBooks · doi:10.1016/b978-0-323-37755-3.50202-6 · Cited by 815 · see citing works
Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis)
Ludwig, J., Dickson, E. R., & McDonald, G. S. A. (1978) · Virchows Archiv A Pathological Anatomy and Histology · doi:10.1007/bf00432479 · Cited by 753 · see citing works
Carey, E. J., Ali, A. H., & Lindor, K. D. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00154-3 · Cited by 735 · see citing works
Cytokine mediated tissue fibrosis
Borthwick, L. A., Wynn, T. A., & Fisher, A. J. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.09.014 · Cited by 375 · see citing works
Mi, S., Li, Z., Yang, H.-Z., Liu, H., Wang, J.-P., Ma, Y.-G., Wang, X.-X., Liu, H.-Z., Sun, W., & Hu, Z.-W. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1004081 · Cited by 370 · see citing works
Epidemiology and natural history of primary biliary cirrhosis in a U.S. community
Kim, W. R., Lindor, K. D., Locke, G. R., Therneau, T. M., Homburger, H. A., Batts, K. P., Yawn, B. P., Petz, J. L., Melton, L. J., & Dickson, E. R. (2000) · Gastroenterology · doi:10.1053/gast.2000.20197 · Cited by 349 · see citing works
PRIMARY BILIARY CIRRHOSIS: IDENTIFICATION OF TWO MAJOR M2 MITOCHONDRIAL AUTOANTIGENS
Yeaman, S. J., Danner, D. J., Mutimer, D., Fussey, S. P. M., James, O., & Bassendine, M. F. (1988) · The Lancet · doi:10.1016/s0140-6736(88)91894-6 · Cited by 292 · see citing works
Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis
The UK Primary Biliary Cirrhosis (PBC) Consortium, Liu, J. Z., The Wellcome Trust Case Control Consortium 3, Almarri, M. A., Gaffney, D. J., Mells, G. F., Jostins, L., Cordell, H. J., Ducker, S. J., Day, D. B., et al. (2012) · Nature Genetics · doi:10.1038/ng.2395 · Cited by 274 · see citing works
Hirschfield, G. M., & Heathcote, E. J. (2010) · Wiley eBooks · doi:10.1002/9781444314403.ch32 · Cited by 260 · see citing works
Hepatic IL-17 responses in human and murine primary biliary cirrhosis
Lan, R. Y. Z., Salunga, T. L., Tsuneyama, K., Lian, Z.-X., Yang, G.-X., Hsu, W., Moritoki, Y., Ansari, A. A., Kemper, C., Price, J., et al. (2009) · Journal of Autoimmunity · doi:10.1016/j.jaut.2008.11.001 · Cited by 202 · see citing works
Case‐control studies of risk factors for primary biliary cirrhosis in two United Kingdom populations
Prince, M. I., Ducker, S. J., & James, O. F. W. (2010) · Gut · doi:10.1136/gut.2009.184218 · Cited by 171 · see citing works
Enhanced apoptosis relates to bile duct loss in primary biliary cirrhosis
Harada, K., Ozaki, S., Gershwin, M. E., & Nakanuma, Y. (1997) · Hepatology · doi:10.1002/hep.510260604 · Cited by 167 · see citing works
Kumada, T., Tsuneyama, K., Hatta, H., Ishizawa, S., & Takano, Y. (2004) · Modern Pathology · doi:10.1038/modpathol.3800165 · Cited by 158 · see citing works
Robertson, H., Kirby, J. A., Yip, W. W., Jones, D. E., & Burt, A. D. (2007) · Hepatology · doi:10.1002/hep.21624 · Cited by 149 · see citing works
Primary Biliary Cirrhosis Showing a High Titer of Autoantibody
Mackay, I. R. (1958) · New England Journal of Medicine · doi:10.1056/nejm195801232580407 · Cited by 147 · see citing works
Sood, S., Gow, P. J., Christie, J. M., & Angus, P. W. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.04.064 · Cited by 140 · see citing works
Yang, H., Cui, B., Liu, H.-Z., Chen, Z., Yan, H., Hua, F., & Hu, Z. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.1.692 · Cited by 103 · see citing works
Vittal, R., Fan, L., Greenspan, D. S., Mickler, E. A., Gopalakrishnan, B., Gu, H., Benson, H. L., Zhang, C., Burlingham, W. J., Cummings, O. W., et al. (2012) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00080.2012 · Cited by 86 · see citing works
Tinmouth, J., Lee, M. M., Wanless, I. R., Tsui, F. W. L., Inman, R. D., & Heathcote, E. J. (2002) · Liver International · doi:10.1046/j.0106-9543.2002.01595.x · Cited by 84 · see citing works
Peters, M. G., Di Bisceglie, A. M., Kowdley, K. V., Flye, N. L., Luketic, V. A., Munoz, S. J., Garcia-Tsao, G., Boyer, T. D., Lake, J. R., Bonacini, M., et al. (2007) · Hepatology · doi:10.1002/hep.21759 · Cited by 70 · see citing works
Qian, C., Jiang, T., Zhang, W., Ren, C., Wang, Q., Qin, Q., Chen, J., Deng, A., & Zhong, R. (2013) · Cytokine · doi:10.1016/j.cyto.2013.07.005 · Cited by 69 · see citing works
Kuroki, T., Seki, S., Kawakita, N., Nakatani, K., Kitada, T., Sakaguchi, H., & Hisa, T. (1996) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf00192434 · Cited by 59 · see citing works
Pathogenesis of Primary Biliary Cirrhosis
Jones, D. E. (2008) · Clinics in Liver Disease · doi:10.1016/j.cld.2008.02.004 · Cited by 58 · see citing works
Ji, X., Li, J., Xu, L., Wang, W., Luo, M., Luo, S., Ma, L., Li, K., Gong, S., He, L., et al. (2013) · Europe PMC (PubMed Central) · Cited by 51 · see citing works
Geoepidemiology, Genetic and Environmental Risk Factors for PBC
Zhang, H., Carbone, M., Lleò, A., & Invernizzi, P. (2015) · Digestive Diseases · doi:10.1159/000440754 · Cited by 38 · see citing works
Zhang, X. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i12.3554 · Cited by 38 · see citing works
Kawata, K., Kobayashi, Y., Gershwin, M. E., & Bowlus, C. L. (2012) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-012-8324-0 · Cited by 38 · see citing works
Chan, A. W. H., Chan, R., Wong, G., Wong, V., Choi, P., Chan, H. L., & To, K. F. (2014) · Histopathology · doi:10.1111/his.12384 · Cited by 30 · see citing works
Berg, P. A. (2011) · Liver International · doi:10.1111/j.1478-3231.2011.02457.x · Cited by 29 · see citing works
Isse, K., Harada, K., Sato, Y., & Nakanuma, Y. (2006) · Pathology International · doi:10.1111/j.1440-1827.2006.01913.x · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review
Lleò, A., Leung, P. S. C., Hirschfield, G. M., & Gershwin, E. M. (2019) · Seminars in Liver Disease · doi:10.1055/s-0039-1697617 · Cited by 138 · see citing works
IL-17 and IL-17-producing cells and liver diseases, with focus on autoimmune liver diseases
Beringer, A., & Miossec, P. (2018) · Autoimmunity Reviews · doi:10.1016/j.autrev.2018.06.008 · Cited by 96 · see citing works
Erice, O., Muñoz-Garrido, P., Vaquero, J., Perugorria, M. J., Fernández‐Barrena, M. G., Sáez, E., Santos‐Laso, Á., Arbelaiz, A., Jiménez-Agüero, R., Fernández‐Irigoyen, J., et al. (2017) · Hepatology · doi:10.1002/hep.29533 · Cited by 96 · see citing works
Paquissi, F. C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01195 · Cited by 93 · see citing works
The Th17/IL-17 Axis and Kidney Diseases, With Focus on Lupus Nephritis
Paquissi, F. C., & Abensur, H. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.654912 · Cited by 89 · see citing works
Immunological abnormalities in patients with primary biliary cholangitis.
Ma, W.-T., & Chen, D.-K. (2019) · Clinical science · doi:10.1042/cs20181123 · Cited by 58 · see citing works
Feng, Y., Chen, Z., Tu, S.-Q., Wei, J.-M., Hou, Y., Kuang, Z., Kang, X.-N., & Ai, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.862415 · Cited by 58 · see citing works
The liver as a central "hub" of the immune system: pathophysiological implications
Ronca, V., Gerussi, A., Collins, P., Parente, A., Oo, Y. H., & Invernizzi, P. (2025) · Physiological Reviews · doi:10.1152/physrev.00004.2023 · Cited by 59 · see citing works
Pan, Y. H., Wang, J., He, L., & Zhang, F. (2021) · Journal of Immunology Research · doi:10.1155/2021/6890423 · Cited by 36 · see citing works
Gabbia, D., Carpi, S., Sarcognato, S., Zanotto, I., Sayaf, K., Colognesi, M., Polini, B., Digiacomo, M., Macchia, M., Nieri, P., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114014 · Cited by 35 · see citing works
Zhang, H., Chen, L., Fan, Z., & Lv, G. (2023) · Liver International · doi:10.1111/liv.15616 · Cited by 32 · see citing works
Lee, C. H. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.10.031 · Cited by 30 · see citing works
Novel Immune Subsets and Related Cytokines: Emerging Players in the Progression of Liver Fibrosis
Wan, M., Han, J., Ding, L., Hu, F., & Gao, P. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.604894 · Cited by 27 · see citing works
Targeting interleukin-17 as a novel treatment option for fibrotic diseases
Sisto, M., & Lisi, S. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm13010164 · Cited by 22 · see citing works
Th17 cells in the liver: balancing autoimmunity and pathogen defense
Taniki, N., Nakamoto, N., Chu, P., Ichikawa, M., Teratani, T., & Kanai∥, T. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00917-9 · Cited by 21 · see citing works
Ishii, A., Shigemura, K., Kitagawa, K., Sung, S., Chen, K., Chiang, Y., Liu, M.-C., & Fujisawa, M. (2020) · Anticancer Research · doi:10.21873/anticanres.14514 · Cited by 20 · see citing works
Berthelot, J., & Puéchal, X. (2017) · Joint Bone Spine · doi:10.1016/j.jbspin.2017.09.007 · Cited by 17 · see citing works
Cichoż‐Lach, H., Grywalska, E., Michalak, A., Kowalik, A., Mielnik, M., & Roliński, J. (2018) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-018-0515-9 · Cited by 17 · see citing works
Tang, S., Jiang, X., Wu, L., Chen, S., Chen, L., Jiang, J., Yan, P., Wang, F., Tu, K., Wang, D., et al. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.08.071 · Cited by 17 · see citing works
Innate immunity of bile and cholangiocytes in primary biliary cholangitis
Chen, R., Sun, Y., Hu, Y., & Tai, W. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1655287 · Cited by 11 · see citing works
Zhang, Y., Zhang, X., Chen, R., Jiao, Z., Shen, B. Q., & Shuai, Z. (2024) · Genomics · doi:10.1016/j.ygeno.2024.110795 · Cited by 9 · see citing works
IL-17 Expression in the Perifollicular Fibrosis in Biopsies From Lichen Planopilaris
Miteva, M. I., Nadji, M., Billero, V., LaSenna, C., Nattkemper, L. A., & Romanelli, P. (2022) · American Journal of Dermatopathology · doi:10.1097/dad.0000000000002316 · Cited by 5 · see citing works
Yang, M., Lin, R., Zhang, X., Li, G., Wang, Q., Li, C., Xiao, Y., Wei, L., & Bi, H. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.127834 · Cited by 5 · see citing works
The Role of miRNA and Long Noncoding RNA in Cholestatic Liver Diseases
Zhang, Y., Liu, Y., Huo, W. J., He, L., Li, B., Wang, H., Meng, F., Duan, C., Zhou, B., Wu, J., et al. (2024) · American Journal Of Pathology · doi:10.1016/j.ajpath.2024.02.006 · Cited by 4 · see citing works
Roles of Non-Coding RNAs in Primary Biliary Cholangitis
Zhang, Y., Jiao, Z., Chen, M., Shen, B., & Shuai, Z. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.915993 · Cited by 4 · see citing works
Zhu, Q., Fu, Y., Qiu, J., Guan, L., Liao, F., Xing, Y., & Zhou, X. (2023) · Gastroenterology report · doi:10.1093/gastro/goae049 · Cited by 2 · see citing works
Berthelot, J., & Puéchal, X. (2017) · Revue du Rhumatisme · doi:10.1016/j.rhum.2017.07.066
IL - 17 et réponse inflammatoire systémique : focus sur le foie et le muscle
Beringer, A. (2018) · theses.fr (ABES) · doi:10.70675/2d9a348ez5879z4d92z938fz1e4047d398bc
Influence of bile acids metabolism on hepatic immunity in mice
Guinot, V. (2022) · theses.fr (ABES) · doi:10.70675/b69bb11eza30fz4874z9af2za6e31b2d5ad8
- Authors
- Huang, Q., Chu, S., Yin, X., Yu, X., Kang, C., Li, X., & Qiu, Y.
- Affiliations
- Nanfang Hospital (CN)
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University
- Venue
- The Tohoku Journal of Experimental Medicine
- Publisher
- Tohoku University Medical Press
- Published
- 2016
- Volume
- 240
- Issue
- 4
- Pages
- 269-275
- ISSN
- 0040-8727 (ISSN-L)
- 1349-3329
- OpenAlex
- W2559513130
- Semantic Scholar
- 5d2310b8f704dcefdd27c9acaf0d9307db8b03b1
- Cited by
- 29
- References
- 34
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 4
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- The Tohoku Journal of Experimental Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- primary biliary cirrhosis, IL-17A, epithelial-mesenchymal transition, vimentin, E-cadherin, inflammatory cytokines, liver fibrosis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Biliary Tract, Cells, Cultured, Epithelial Cells, Female, Humans, Liver, Liver Cirrhosis, Biliary, Male, Middle Aged, Antigens, CD, Cadherins, Interleukin-17, Cell Shape, Receptors, Interleukin-17, Young Adult, Epithelial-Mesenchymal Transition
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