Exosome-mediated activation of Toll-like receptor 3 in stellate cells stimulates interleukin-17 production by γδ T cells in liver fibrosis
Open accessAbstract
During liver injury, hepatocytes secrete exosomes that include diverse types of self‐RNAs. Recently, self‐noncoding RNA has been recognized as an activator of Toll‐like receptor 3 (TLR3). However, the roles of hepatic exosomes and TLR3 in liver fibrosis are not yet fully understood. Following acute liver injury and early‐stage liver fibrosis induced by a single or 2‐week injection of carbon tetrachloride (CCl 4), increased interleukin (IL)‐17A production was detected primarily in hepatic γδ T cells in wild‐type (WT) mice. However, liver fibrosis and IL‐17A production by γδ T cells were both significantly attenuated in TLR3 knockout (KO) mice compared with WT mice. More interestingly, IL‐17A‐producing γδ T cells were in close contact with activated hepatic stellate cells (HSCs), suggesting a role for HSCs in IL‐17A production by γδ T cells.In vitro treatments with exosomes derived from CCl 4‐treated hepatocytes significantly increased the expression of IL‐17A, IL‐1β, and IL‐23 in WT HSCs but not in TLR3 KO HSCs. Furthermore, IL‐17A production by γδ T cells was substantially increased upon coculturing with exosome‐treated WT HSCs or conditioned medium from TLR3‐activated WT HSCs. However, similar increases were not detected when γδ T cells were cocultured with exosome‐treated HSCs from IL‐17A KO or TLR3 KO mice. Using reciprocal bone marrow transplantation between WT and TLR3 KO mice, we found that TLR3 deficiency in HSCs contributed to decreased IL‐17A production by γδ T cells, as well as liver fibrosis.Conclusion: In liver injury, the exosome‐mediated activation of TLR3 in HSCs exacerbates liver fibrosis by enhancing IL‐17A production by γδ T cells, which might be associated with HSC stimulation by unknown self‐TLR3 ligands from damaged hepatocytes. Therefore, TLR3 might be a novel therapeutic target for liver fibrosis. (H epatology 2016;64:616‐631)
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hepatic γδ T cells promote IL-17 release in mouse models of liver fibrosis, indicating a profibrogenic function.
“Although hepatic γδ T cells promote IL-17 release in mouse models of liver fibrosis, and therefore indicate a profibrogenic function (76, 77)”
From Immunoregulation of Liver Fibrosis: New Opportunities for Antifibrotic Therapy (2024) · cites this paper as [76]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145 · see citing works
Extracellular vesicles: biology and emerging therapeutic opportunities
EL Andaloussi, S., Mäger, I., Breakefield, X. O., & Wood, M. J. A. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3978 · Cited by 3,254 · see citing works
Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A., & Sallusto, F. (2007) · Nature Immunology · doi:10.1038/ni1496 · Cited by 1,857 · see citing works
Hepatotoxicity and Mechanism of Action of Haloalkanes: Carbon Tetrachloride as a Toxicological Model
Weber, L. W. D., Boll, M., & Stampfl, A. (2003) · Critical Reviews in Toxicology · doi:10.1080/713611034 · Cited by 1,780 · see citing works
Sutton, C. E., Lalor, S. J., Sweeney, C. M., Brereton, C. F., Lavelle, E. C., & Mills, K. H. G. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.001 · Cited by 1,553 · see citing works
The Liver as an Immunological Organ
Racanelli, V., & Rehermann, B. (2006) · Hepatology · doi:10.1002/hep.21060 · Cited by 1,377 · see citing works
Mechanisms of carbon tetrachloride toxicity
Recknagel, R. O., Glende, E. A., Dolak, J. A., & Waller, R. L. (1989) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(89)90050-8 · Cited by 1,234 · see citing works
mRNA is an endogenous ligand for toll-like receptor 3
Karikó, K., Ni, H., Capodici, J., Lamphier, M., & Weissman, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310175200 · Cited by 1,062 · see citing works
Hepatic inflammation and fibrosis: Functional links and key pathways
Seki, E., & Schwabe, R. F. (2015) · Hepatology · doi:10.1002/hep.27332 · Cited by 972 · see citing works
Liver: An organ with predominant innate immunity
Gao, B., Jeong, W.-I., & Tian, Z. (2008) · Hepatology · doi:10.1002/hep.22034 · Cited by 952 · see citing works
Self-citationPathobiology of liver fibrosis: a translational success story
Lee, Y. A., Wallace, M. C., & Friedman, S. L. (2015) · Gut · doi:10.1136/gutjnl-2014-306842 · Cited by 894 · see citing works
Self-citationExosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Liver Fibrosis
Li, T., Yan, Y., Wang, B., Qian, H., Zhang, X., Shen, L., Wang, M., Zhou, Y., Zhu, W. Z., Li, W., et al. (2012) · Stem Cells and Development · doi:10.1089/scd.2012.0395 · Cited by 853 · see citing works
Martin, B., Hirota, K., Cua, D. J., Stockinger, B., & Veldhoen, M. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.020 · Cited by 822 · see citing works
Meng, F., Wang, K., Aoyama, T., Grivennikov, S. I., Paik, Y., Scholten, D., Cong, M., Iwaisako, K., Liu, X., Zhang, M., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.05.049 · Cited by 711 · see citing works
Ultraviolet radiation damages self noncoding RNA and is detected by TLR3
Bernard, J. J., Cowing-Zitron, C., Nakatsuji, T., Muehleisen, B., Muto, J., Borkowski, A. W., Martinez, L., Greidinger, E. L., Yu, B., & Gallo, R. L. (2012) · Nature Medicine · doi:10.1038/nm.2861 · Cited by 408 · see citing works
Tan, Z., Qian, X., Jiang, R., Liu, Q., Wang, Y., Chen, C., Wang, X., Ryffel, B., & Sun, B. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203013 · Cited by 330 · see citing works
Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases
Masyuk, A. I., Masyuk, T. V., & LaRusso, N. F. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.028 · Cited by 283 · see citing works
Jeong, W., Park, O., Radaeva, S., & Gao, B. (2006) · Hepatology · doi:10.1002/hep.21419 · Cited by 274 · see citing works
Self-citationChen, L., Charrier, A., Zhou, Y., Chen, R., Yu, B., Agarwal, K., Tsukamoto, H., Lee, J. L., Paulaitis, M. E., & Brigstock, D. R. (2013) · Hepatology · doi:10.1002/hep.26768 · Cited by 264 · see citing works
Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9
Watanabe, A., Hashmi, A., Gomes, D. A., Town, T., Badou, A., Flavell, R. A., & Mehal, W. Z. (2007) · Hepatology · doi:10.1002/hep.21867 · Cited by 262 · see citing works
Witek, R. P., Yang, L., Liu, R., Jung, Y., Omenetti, A., Syn, W., Choi, S. S., Cheong, Y., Fearing, C. M., Agboola, K. M., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.09.066 · Cited by 210 · see citing works
The SKIV2L RNA exosome limits activation of the RIG-I-like receptors
Eckard, S. C., Rice, G., Fabre, A., Badens, C., Gray, E. E., Hartley, J., Crow, Y. J., & Stetson, D. B. (2014) · Nature Immunology · doi:10.1038/ni.2948 · Cited by 199 · see citing works
Hammerich, L., Bangen, J. M., Govaere, O., Zimmermann, H. W., Gassler, N., Huss, S., Liedtke, C., Prinz, I., Lira, S. A., Luedde, T., et al. (2014) · Hepatology · doi:10.1002/hep.26697 · Cited by 190 · see citing works
Wang, X., Sun, R., Wei, H., & Tian, Z. (2012) · Hepatology · doi:10.1002/hep.25982 · Cited by 186 · see citing works
Jiang, J. X., Mikami, K., Venugopal, S. K., Li, Y., & Torok, N. J. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.03.024 · Cited by 157 · see citing works
Knockaert, L., Berson, A., Ribault, C., Prost, P.-E., Fautrel, A., Pajaud, J., Lepage, S., Lucas‐Clerc, C., Bégué, J., Fromenty, B., et al. (2011) · Laboratory Investigation · doi:10.1038/labinvest.2011.193 · Cited by 132 · see citing works
Involvement of natural killer cells in PolyI:C-induced liver injury
Dong, Z., Wei, H., Sun, R., Hu, Z., Gao, B., & Tian, Z. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.08.021 · Cited by 97 · see citing works
Byun, J.-S., Suh, Y., Yi, H., Lee, Y., & Jeong, W. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.09.016 · Cited by 82 · see citing works
Self-citationCD11b+ Gr1+ bone marrow cells ameliorate liver fibrosis by producing interleukin-10 in mice
Suh, Y., Kim, J. K., Byun, J.-S., Yi, H., Lee, Y., Eun, H. S., Kim, S. Y., Han, K., Lee, K. S., Duester, G., et al. (2012) · Hepatology · doi:10.1002/hep.25817 · Cited by 75 · see citing works
Self-citationZhao, N., Hao, J., Ni, Y., Luo, W., Liang, R., Cao, G., Zhao, Y., Wang, P., Zhao, L., Tian, Z., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101315 · Cited by 67 · see citing works
Yi, H., Lee, Y., Byun, J.-S., Seo, W., Jeong, J., Park, O., Duester, G., Haseba, T., Kim, S. C., Park, K. G., et al. (2014) · Hepatology · doi:10.1002/hep.27137 · Cited by 67 · see citing works
Self-citationInteraction of hepatic stellate cells with diverse types of immune cells: Foe or friend?
Yi, H., & Jeong, W. (2013) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12017 · Cited by 51 · see citing works
Self-citationLibonati, M., Carsana, A., & Furia, A. (1980) · Molecular and Cellular Biochemistry · doi:10.1007/bf00225848 · Cited by 46 · see citing works
Wilson, C. L., Mann, J., Walsh, M., Perrugoria, M. J., Oakley, F., Wright, M. C., Brignole, C., Di Paolo, D., Perri, P., Ponzoni, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0083391 · Cited by 31 · see citing works
Binding of carbon tetrachloride metabolites to rat hepatic mitochondrial DNA
Levy, G. N., & Brabec, M. J. (1984) · Toxicology Letters · doi:10.1016/0378-4274(84)90071-7 · Cited by 30 · see citing works
Toll-Like Receptor 3 in Liver Diseases
Yin, S., & Gao, B. (2010) · Gastroenterology Research and Practice · doi:10.1155/2010/750904 · Cited by 27 · see citing works
Kim, H., Jang, M.-J., Kang, M., & Han, Y. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq476 · Cited by 24 · see citing works
Self-citationKantarjian, H., Barlogie, B., Pershouse, M., Swartzendruber, D., Keating, M. J., McCredie, K., & Freireich, E. (1985) · Blood · doi:10.1182/blood.v66.1.39.39 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of hepatic stellate cell activation
Tsuchida, T., & Friedman, S. L. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.38 · Cited by 2,909 · see citing works
Hepatic stellate cells as key target in liver fibrosis
Higashi, T., Friedman, S. L., & Hoshida, Y. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.05.007 · Cited by 1,485 · see citing works
Hepatic inflammatory responses in liver fibrosis
Hammerich, L., & Tacke, F. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00807-x · Cited by 803 · see citing works
The Liver as an Endocrine Organ—Linking NAFLD and Insulin Resistance
Watt, M. J., Miotto, P. M., De Nardo, W., & Montgomery, M. K. (2019) · Endocrine Reviews · doi:10.1210/er.2019-00034 · Cited by 615 · see citing works
The Power of Plasticity—Metabolic Regulation of Hepatic Stellate Cells
Trivedi, P., Wang, S., & Friedman, S. L. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2020.10.026 · Cited by 427 · see citing works
T Cells in Fibrosis and Fibrotic Diseases
Zhang, M., & Zhang, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01142 · Cited by 333 · see citing works
Wu, Q. J., Zhou, L., Lv, D., Zhu, X., & Tang, H. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0739-0 · Cited by 282 · see citing works
Kim, S. Y., Jeong, J., Kim, S. J., Seo, W., Kim, M., Choi, W., Yoo, W., Lee, J. H., Shim, Y., Yi, H., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02325-2 · Cited by 258 · see citing works
Self-citationOxidative Stress Is a Key Modulator in the Development of Nonalcoholic Fatty Liver Disease
Ma, Y., Lee, G., Heo, S.-Y., & Roh, Y. (2021) · Antioxidants · doi:10.3390/antiox11010091 · Cited by 225 · see citing works
Liver governs adipose remodelling via extracellular vesicles in response to lipid overload
Zhao, Y., Zhao, M., Jiang, S., Wu, J., Liu, J., Yuan, X., Shen, D., Zhang, J., Zhou, N., He, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14450-6 · Cited by 172 · see citing works
Intercellular crosstalk of hepatic stellate cells in liver fibrosis: New insights into therapy
Cai, X., Wang, J., Wang, J., Zhou, Q., Yang, B., He, Q., & Weng, Q. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104720 · Cited by 167 · see citing works
Zhang, X.-W., Zhou, J.-C., Peng, D., Hua, F., Li, K., Yu, J.-J., Lv, X.-X., Cui, B., Liu, S.-S., Yu, J.-M., et al. (2020) · Autophagy · doi:10.1080/15548627.2019.1635383 · Cited by 166 · see citing works
Interleukin-36γ–producing macrophages drive IL-17–mediated fibrosis
Sommerfeld, S. D., Cherry, C., Schwab, R. M., Chung, L., Maestas, D. R., Laffont, P., Stein, J. E., Tam, A. J., Ganguly, S., Housseau, F., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aax4783 · Cited by 157 · see citing works
The spleen in liver cirrhosis: revisiting an old enemy with novel targets
Li, L., Duan, M., Chen, W., Jiang, A., Li, X., Yang, J. J., & Li, Z. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1214-8 · Cited by 159 · see citing works
McCommis, K. S., Hodges, W. T., Brunt, E. M., Nalbantoglu, I., McDonald, W. G., Holley, C. L., Fujiwara, H., Schaffer, J. E., Colca, J. R., & Finck, B. N. (2016) · Hepatology · doi:10.1002/hep.29025 · Cited by 138 · see citing works
Immunopathobiology and therapeutic targets related to cytokines in liver diseases
He, Y., Hwang, S., Ahmed, Y. A., Feng, D., Li, N., Ribeiro, M. D. C., Lafdil, F., Kisseleva, T., Szabó, G., & Gao, B. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00580-w · Cited by 136 · see citing works
Extracellular vesicles and particles impact the systemic landscape of cancer
Lucotti, S., Kenific, C. M., Zhang, H., & Lyden, D. C. (2022) · The EMBO Journal · doi:10.15252/embj.2021109288 · Cited by 134 · see citing works
Pathophysiology and Treatment Options for Hepatic Fibrosis: Can It Be Completely Cured?
Khanam, A., Saleeb, P. G., & Kottilil, S. (2021) · Cells · doi:10.3390/cells10051097 · Cited by 132 · see citing works
Lee, J. H., Shim, Y., Seo, W., Kim, M., Choi, W., Kim, H., Kim, Y. E., Yang, K., Ryu, T., Jeong, J., et al. (2019) · Hepatology · doi:10.1002/hep.31041 · Cited by 122 · see citing works
Self-citationChen, L., Yao, X., Yao, H., Ji, Q., Ding, G., & Liu, X. (2020) · The FASEB Journal · doi:10.1096/fj.201902307rrr · Cited by 123 · see citing works
Role of Metabolism in Hepatic Stellate Cell Activation and Fibrogenesis
Hou, W., & Syn, W. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00150 · Cited by 121 · see citing works
GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury
Chung, H. K., Kim, J. T., Kim, H.-W., Kwon, M., Kim, S. Y., Shong, M., Kim, K. S., & Yi, H. (2017) · Scientific Reports · doi:10.1038/s41598-017-17574-w · Cited by 111 · see citing works
Self-citationLiu, J., Chen, T., Lei, P., Tang, X., & Huang, P. (2019) · International Journal of Medical Sciences · doi:10.7150/ijms.35369 · Cited by 110 · see citing works
Wu, J., Dong, T., Chen, T., Sun, J., Luo, J., He, J., Wei, L., Zeng, B., Zhang, H., Li, W., et al. (2019) · Metabolism · doi:10.1016/j.metabol.2019.154006 · Cited by 103 · see citing works
Shi, D., Lv, L., Fang, D., Wu, W., Hu, C., Xu, L., Chen, Y., Guo, J., Hu, X., Li, A., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-07091-1 · Cited by 100 · see citing works
Zhang, Q., Qu, Y., Zhang, Q., Li, F., Li, B., Li, Z., Dong, Y., Lu, L., & Cai, X. (2022) · Cell Biology and Toxicology · doi:10.1007/s10565-021-09684-z · Cited by 103 · see citing works
Liver-Derived Exosomes and Their Implications in Liver Pathobiology
Sung, S., Kim, J., & Jung, Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123715 · Cited by 100 · see citing works
Zonneveld, M. I., van Herwijnen, M. J. C., Fernandez-Gutierrez, M. M., Giovanazzi, A., de Groot, A. M., Kleinjan, M., van Capel, T. M. M., Sijts, A. J. A. M., Taams, L. S., Garssen, J., et al. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12071 · Cited by 100 · see citing works
Liu, X., Tan, S., Liu, H., Jiang, J., Wang, X., Li, L., & Wu, B. (2022) · Hepatology · doi:10.1002/hep.32662 · Cited by 97 · see citing works
Paquissi, F. C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01195 · Cited by 93 · see citing works
Toll-like receptors and metabolic (dysfunction)-associated fatty liver disease
Khanmohammadi, S., & Kuchay, M. S. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106507 · Cited by 93 · see citing works
Combatting Fibrosis: Exosome‐Based Therapies in the Regression of Liver Fibrosis
Chen, L., Brenner, D. A., & Kisseleva, T. (2018) · Hepatology Communications · doi:10.1002/hep4.1290 · Cited by 91 · see citing works
Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer
Chen, Y.-Y., & Tian, Z. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-00561-z · Cited by 83 · see citing works
Recent advances of sterile inflammation and inter-organ cross-talk in alcoholic liver disease
Shim, Y., & Jeong, W. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0438-5 · Cited by 81 · see citing works
Self-citationObeticholic acid protects against carbon tetrachloride‐induced acute liver injury and inflammation
Zhang, D.-G., Zhang, C., Wang, J.-X., Wang, B.-W., Wang, H., Zhang, Z.-H., Chen, Y.-H., Lu, Y., Tao, L., Wang, J.-Q., et al. (2017) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2016.11.006 · Cited by 75 · see citing works
Pathways of production and delivery of hepatocyte exosomes
Chen, L., Chen, R., Kemper, S., & Brigstock, D. R. (2017) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-017-0421-7 · Cited by 78 · see citing works
Advances on liver cell‐derived exosomes in liver diseases
Yan, J., Xu, P., Shi, H., Chen, D., & Shi, H. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16123 · Cited by 76 · see citing works
Progranulin attenuates liver fibrosis by downregulating the inflammatory response
Yoo, W., Lee, J., Noh, K. H., Lee, S., Jung, D., Kabir, M. H., Park, D., Lee, C., Kwon, K., Kim, J.-S., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1994-2 · Cited by 71 · see citing works
Self-citationCrosstalk network among multiple inflammatory mediators in liver fibrosis
Zhangdi, H., Su, S.-B., Wang, F., Liang, Z., Yan, Y.-D., Qin, S., & Jiang, H.-X. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i33.4835 · Cited by 70 · see citing works
Crosstalk between hepatic stellate cells and surrounding cells in hepatic fibrosis
Yang, F., Li, H., Li, Y., Hao, Y., Wang, C., Jia, P. P., Chen, X., Ma, S., & Xiao, Z. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108051 · Cited by 71 · see citing works
The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression
Chen, D., Le, T. H., Shahidipour, H., Read, S. A., & Ahlenstiel, G. (2019) · Cells · doi:10.3390/cells8111324 · Cited by 67 · see citing works
Liu, M., Hu, Y., Yuan, Y., Tian, Z., & Zhang, C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00477 · Cited by 65 · see citing works
Wang, J., Pan, W., Wang, Y., Lei, W., Feng, B., Du, C., & Wang, X. (2017) · Drug Delivery · doi:10.1080/10717544.2017.1399301 · Cited by 66 · see citing works
The contrasting roles of inflammasomes in cancer.
He, Q., Fu, Y., Tian, D., & Yan, W. (2018) · Europe PMC (PubMed Central) · Cited by 64 · see citing works
Shi, J., Zhao, J., Zhang, X., Cheng, Y., Hu, J., Li, Y., Zhao, X., Shang, Q., Sun, Y., Tu, B., et al. (2017) · Scientific Reports · doi:10.1038/srep44544 · Cited by 64 · see citing works
Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics
Brigstock, D. R. (2021) · Cells · doi:10.3390/cells10071596 · Cited by 63 · see citing works
Liver fibrosis: Extracellular vesicles mediated intercellular communication in perisinusoidal space
Ezhilarasan, D., Perumal, E., Raghunandhakumar, S., & Najimi, M. (2021) · Hepatology · doi:10.1002/hep.32239 · Cited by 63 · see citing works
Dai, X., Chen, C., Xue, J., Xiao, T., Mostofa, G., Wang, D., Chen, X., Xu, H., Sun, Q., Li, J., et al. (2019) · Toxicology Letters · doi:10.1016/j.toxlet.2019.09.008 · Cited by 63 · see citing works
Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues
Teschke, R., & Uetrecht, J. (2021) · Annals of Translational Medicine · doi:10.21037/atm-2020-ubih-05 · Cited by 61 · see citing works
Choi, W., Ryu, T., Lee, J. H., Shim, Y., Kim, M., Kim, H., Kim, Y. E., Yang, K., Kim, K., Choi, S. E., et al. (2021) · Hepatology · doi:10.1002/hep.31875 · Cited by 60 · see citing works
Self-citationExosomes and Obesity-Related Insulin Resistance
Lei, L.-M., Lin, X., Xu, F., Shan, S., Guo, B., Li, F., Zheng, M.-H., Wang, Y., Xu, Q.-S., & Yuan, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.651996 · Cited by 57 · see citing works
Shi, Y., Du, L., Lv, D., Li, Y., Zhang, Z., Huang, X., & Tang, H. (2021) · Journal of Gastroenterology · doi:10.1007/s00535-021-01765-4 · Cited by 56 · see citing works
Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases
Zhu, J., Wang, S., Yang, D., Xu, W., & Qian, H. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-01921-3 · Cited by 60 · see citing works
Liu, Y., Zheng, Y., Yang, Y., Liu, K., Wu, J., Gao, P., & Zhang, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1133297 · Cited by 53 · see citing works
Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis
Tavasolian, F., Lively, S. S., Pastrello, C., Tang, M., Lim, M., Pacheco, A., Qaiyum, Z., Yau, E., Baskurt, Z., Jurišica, I., et al. (2023) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2022-223791 · Cited by 53 · see citing works
Zhu, M., Liu, X., Li, W., & Wang, L. (2020) · Human & Experimental Toxicology · doi:10.1177/0960327120931152 · Cited by 45 · see citing works
RetractedLee, Y., & Kim, J. (2022) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2021.0390 · Cited by 44 · see citing works
Self-citationLi, X., Chen, R., Kemper, S., & Brigstock, D. R. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00368 · Cited by 44 · see citing works
Wang, X., & Tian, Z. (2018) · Frontiers of Medicine · doi:10.1007/s11684-017-0584-x · Cited by 42 · see citing works
Immune Dysfunction and Infection Risk in Advanced Liver Disease
McGettigan, B. M., Hernández‐Tejero, M., Malhi, H., & Shah, V. H. (2025) · Gastroenterology · doi:10.1053/j.gastro.2024.08.046 · Cited by 44 · see citing works
Lü, J., Zhang, J., Wang, Y., & Sun, Q. X. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061729 · Cited by 40 · see citing works
Holman, N. S., Church, R. J., Nautiyal, M., Rose, K., Thacker, S. E., Otieno, M. A., Wolf, K., LeCluyse, E. L., Watkins, P. B., & Mosedale, M. (2019) · Toxicological Sciences · doi:10.1093/toxsci/kfz112 · Cited by 40 · see citing works
Abdelnabi, M. N., Hassan, G. S., & Shoukry, N. H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1437046 · Cited by 38 · see citing works
Exosomes: Carriers of Pro-Fibrotic Signals and Therapeutic Targets in Fibrosis
Li, M., Jiang, M., Meng, J., & Tao, L. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191209161443 · Cited by 38 · see citing works
Fiore, E. J., Domínguez, L. M., Bayo, J., García, M. G., & Mazzolini, G. D. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i23.2427 · Cited by 37 · see citing works
Extracellular Vesicles as Biomarkers in Liver Disease
Múñoz‐Hernández, R., Rojas, Á., Gato, S., Gallego, J., Gil‐Gómez, A., Castro, M. J., Ampuero, J., & Romero‐Gómez, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416217 · Cited by 34 · see citing works
The role of the interleukin family in liver fibrosis
Zhang, Z., Wang, J., Li, H., Niu, Q. F., Tao, Y., Zhao, X., Zeng, Z., & Dong, H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1497095 · Cited by 34 · see citing works
Zayed, R. A., Omran, D., Mokhtar, D. A., Zakaria, Z. A., Ezzat, S., Soliman, M. A., Mobarak, L., El-Sweesy, H., & Emam, G. M. (2017) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.16-0644 · Cited by 34 · see citing works
Role of γδT cells in liver diseases and its relationship with intestinal microbiota
Zhou, Q.-H., Wu, F.-T., Pang, L., Zhang, T.-B., & Chen, Z. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i20.2559 · Cited by 29 · see citing works
Liver Regeneration and Immunity: A Tale to Tell
Di-Iacovo, N., Pieroni, S., Piobbico, D., Castelli, M., Scopetti, D., Ferracchiato, S., Fazia, M. A. D., & Servillo, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021176 · Cited by 36 · see citing works
Gut microbiota in MAFLD: therapeutic and diagnostic implications
Alghamdi, W., Mosli, M. H., & Alqahtani, S. A. (2024) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188241242937 · Cited by 32 · see citing works
Wang, W., Li, F., Lai, X., Liu, H., Wu, S., Han, Y., & Shen, Y. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00536-7 · Cited by 32 · see citing works
Self-citationInnate-like T cells in liver disease.
Yang, A. Y.-P., Wistuba-Hamprecht, K., Greten, T., & Ruf, B. (2024) · Trends in immunology · doi:10.1016/j.it.2024.05.008 · Cited by 30 · see citing works
Exosomes As Mediators and Biomarkers in Fibrosis
Qin, X.-J., Zhang, J., & Wang, R. (2020) · Biomarkers in Medicine · doi:10.2217/bmm-2019-0368 · Cited by 29 · see citing works
Li, X., Chen, R., Kemper, S., & Brigstock, D. R. (2020) · Cells · doi:10.3390/cells9020290 · Cited by 28 · see citing works
Structural and Functional Characterization of Fibronectin in Extracellular Vesicles From Hepatocytes
Li, X., Chen, R., Kemper, S., & Brigstock, D. R. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.640667 · Cited by 28 · see citing works
Exosomes: Nomenclature, Isolation, and Biological Roles in Liver Diseases
Park, S. H., Lee, E. K., Yim, J., Lee, M. H., Lee, E., Lee, Y., & Seo, W. (2023) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2022.161 · Cited by 28 · see citing works
Self-citationPotential applications of using tissue-specific EVs in targeted therapy and vaccinology
Lehmann, T. P., Golik, M., Olejnik, J., Łukaszewska, M., Markowska, D., Drożdżyńska, M., Kotecki, A., Głowacki, M., & Jagodziński, P. P. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115308 · Cited by 28 · see citing works
ENMD-1068 inhibits liver fibrosis through attenuation of TGF-β1/Smad2/3 signaling in mice
Sun, Q. X., Wang, Y., Zhang, J., & Lü, J. (2017) · Scientific Reports · doi:10.1038/s41598-017-05190-7 · Cited by 28 · see citing works
Zhang, N., Yao, H., Zhang, Z., Li, Z., Chen, X., Zhao, Y., Ju, R., He, J., Pan, H., Liu, X., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1131588 · Cited by 26 · see citing works
Tissue-resident and innate-like T cells in patients with advanced chronic liver disease
Ibidapo-Obe, O., & Bruns, T. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100812 · Cited by 25 · 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
A review of the effect of exosomes from different cells on liver fibrosis
Hu, X., Ge, Q.-L., Zhang, Y., Li, B., Cheng, E., Wang, Y.-H., & Huang, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114415 · Cited by 25 · see citing works
The Role of Exosomes in Viral Hepatitis and Its Associated Liver Diseases
Zhou, H., Yan, Z., Yuan, Y., Chen, X., & Jiang, N. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.782485 · Cited by 24 · see citing works
Lin, D., Sun, Z., Jin, Z., Lei, L., Liu, Y., Hu, B., Wang, B., Shen, Y. H., & Wang, Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00773 · Cited by 24 · see citing works
Retinoic Acid: A New Old Friend of IL-17A in the Immune Pathogeny of Liver Fibrosis
Kartasheva-Ebertz, D., Pol, S., & Lagaye, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.691073 · Cited by 24 · see citing works
ChemPert: mapping between chemical perturbation and transcriptional response for non-cancer cells
Zheng, M., Okawa, S., Bravo, M., Chen, F., Martínez‐Chantar, M. L., & del Sol, A. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac862 · Cited by 23 · see citing works
Zhang, H., Ju, B., Zhang, X., Zhu, Y., Nie, Y., Xu, Y., & Lei, Q. (2016) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12749 · Cited by 23 · see citing works
Ipsen, D. H., & Tveden‐Nyborg, P. (2021) · Biomedicines · doi:10.3390/biomedicines9010093 · Cited by 22 · see citing works
Hepatotoxicity assessment of Rhizoma Paridis in adult zebrafish through proteomes and metabolome
Jia, Z., Zhao, C., Wang, M., Zhao, X., Zhang, W., Han, T., Xia, Q., Han, Z., Lin, R., & Li, X.-R. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109558 · Cited by 21 · see citing works
Kakizaki, M., Yamamoto, Y., Nakayama, S., Kameda, K., Nagashima, E., Ito, M., Suyama, T. L., Matsuzaki, Y., Chiba, T., Sumiyoshi, H., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04204-7 · Cited by 21 · see citing works
The Role of Extracellular Vesicles in Liver Pathogenesis
Liu, G., & Yin, X. (2022) · American Journal Of Pathology · doi:10.1016/j.ajpath.2022.06.007 · Cited by 21 · see citing works
Extracellular vesicles: catching the light of intercellular communication in fibrotic liver diseases
Li, Y., Wu, J., Liu, R., Zhang, Y., & Li, X. (2022) · Theranostics · doi:10.7150/thno.77256 · Cited by 21 · see citing works
Ni, M., Gu, J., Rao, J., Zhang, Y., Ding, Z., Wang, X., & Lü, L. (2016) · Hepatology · doi:10.1002/hep.28729 · Cited by 21 · see citing works
Cross-talk between hepatic stellate cells and T lymphocytes in liver fibrosis
Li, H., Ding, P., Peng, B., & Ming, Y. (2021) · Hepatobiliary & pancreatic diseases international · doi:10.1016/j.hbpd.2021.04.007 · Cited by 20 · see citing works
Role of Extracellular Vesicles in Liver Diseases
Tamási, V., Németh, K., & Csala, M. (2023) · Life · doi:10.3390/life13051117 · Cited by 20 · see citing works
Sun, D., Li, W., Ding, D., Tan, K., Ding, W., Wang, Z., Fu, S., Hou, G., Zhou, W., & Gu, F. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01995-4 · Cited by 20 · see citing works
Deciphering the Contribution of γδ T Cells to Outcomes in Transplantation
McCallion, O., Hester, J., & Issa, F. (2018) · Transplantation · doi:10.1097/tp.0000000000002335 · Cited by 20 · see citing works
The Tumor Microenvironment of Hepatocellular Carcinoma: Untying an Intricate Immunological Network
Volponi, C., Gazzillo, A., & Bonavita, E. (2022) · Cancers · doi:10.3390/cancers14246151 · Cited by 19 · see citing works
- Authors
- Seo, W., Eun, H. S., Kim, S. Y., Yi, H., Lee, Y., Park, S., Jang, M., Jo, E., Kim, S. C., Han, Y., Park, K., & Jeong, W.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- Chungnam National University (KR)
- Korea University (KR)
- Seoul National University (KR)
- Kyungpook National University (KR)
- Corresponding author
- Jeong, Won‐Il
- ORCID
- Venue
- Hepatology
- Published
- 2016-06-29
- Volume
- 64
- Issue
- 2
- Pages
- 616-631
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W2363676876
- Cited by
- 175
- References
- 38
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 19 · 2023: 17 · 2022: 23 · 2021: 24 · 2020: 25 · 2019: 19 · 2018: 10 · 2017: 13 · 2016: 5
- FWCI
- 11.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation (2011-0031955)
- Ministry of Science, ICT and Future Planning (NFR-2015R1A2A1A10055551, 2011-0031955)
- Rural Development Administration
- National Research Foundation of Korea (NRF-2014, 2015R1A2A1A10055551, 2011-0031955)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- liver fibrosis, exosomes, TLR3, hepatic stellate cells, γδ T cells, IL-17A, carbon tetrachloride, IL-1β, IL-23, bone marrow transplantation, acute liver injury
- MeSH terms
- Animals, Carbon Tetrachloride Poisoning, Liver Cirrhosis, Male, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Receptors, Antigen, T-Cell, gamma-delta, Interleukin-17, Toll-Like Receptor 3, Hepatic Stellate Cells, Exosomes, Nuclear Receptor Subfamily 1, Group F, Member 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
