The DOI matches its Crossref record; 52 of the 54 references it cites were found in a registry or an index.
Interleukin-33-Dependent Innate Lymphoid Cells Mediate Hepatic Fibrosis
Open accessAbstract
Liver fibrosis is a consequence of chronic liver diseases and thus a major cause of mortality and morbidity. Clinical evidence and animal studies suggest that local tissue homeostasis is disturbed due to immunological responses to chronic hepatocellular stress. Poorly defined stress-associated inflammatory networks are thought to mediate gradual accumulation of extracellular-matrix components, ultimately leading to fibrosis and liver failure. Here we have reported that hepatic expression of interleukin-33 (IL-33) was both required and sufficient for severe hepatic fibrosis in vivo. We have demonstrated that IL-33's profibrotic effects related to activation and expansion of liver resident innate lymphoid cells (ILC2). We identified ILC2-derived IL-13, acting through type-II IL-4 receptor-dependent signaling via the transcription factor STAT6 and hepatic stellate-cell activation, as a critical downstream cytokine of IL-33-dependent pathologic tissue remodeling and fibrosis. Our data reveal key immunological networks implicated in hepatic fibrosis and support the concept of modulation of IL-33 bioactivity for therapeutic purposes.
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“Additionally, ILC2s (via IL-33), T cells (via IL-17), B cells (immunoglobulin independent), Tregs (via amphiregulin) and platelets have been suggested to directly promote HSC activation [197, 237, 242–245].”
From Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells (2025) · cites this paper as [242]
In the citing paper
“Together, these data suggest complex roles for IL-33 and ILC-2 in NASH and possibly thresholds for IL-33 that need to be surpassed to modulate fibrosis.”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [87]
In the citing paper
“IL-33-mediated expansion of ILC2s was shown to promote toxin-induced liver fibrosis through an IL-13-IL4R-STAT6 pathway.87”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [87]
In the citing paper
“a modified version of this model in which bleomycin is injected intra-dermally rather than intra-tracheally over several weeks uncovered a substantial role for IL-4R signaling in the development of pulmonary fibrosis141”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [141]
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Bataller, R., & Brenner, D. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24282 · Cited by 4,958
Schmitz, J., Owyang, A. M., Oldham, E. R., Song, Y., Murphy, E., McClanahan, T. K., Zurawski, G., Moshrefi, M., Qin, J., Li, X., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.09.015 · Cited by 3,773
Mechanisms of Hepatic Fibrogenesis
Friedman, S. L. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.003 · Cited by 2,687
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity
Neill, D. R., Wong, S. H., Bellosi, A., Flynn, R. J., Daly, M. G., Langford, T. K. A., Bucks, C. M., Kane, C. M., Fallon, P. G., Pannell, R., et al. (2010) · Nature · doi:10.1038/nature08900 · Cited by 2,079
Self-citationInnate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells
Moro, K., Yamada, T., Tanabe, M., Takeuchi, T., Ikawa, T., Kawamoto, H., Furusawa, J.-I., Ohtani, M., Fujii, H., & Koyasu, S. (2009) · Nature · doi:10.1038/nature08636 · Cited by 1,994
Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA
Liu, F., Song, Y. K., & Liu, D. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300947 · Cited by 1,728
Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus
Monticelli, L. A., Sonnenberg, G. F., Abt, M. C., Alenghat, T., Ziegler, C. G. K., Doering, T. A., Angelosanto, J., Laidlaw, B. J., Yang, C. Y., Sathaliyawala, T., et al. (2011) · Nature Immunology · doi:10.1038/ni.2131 · Cited by 1,327
Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus
Monticelli (2011) · PubMed · doi:10.1031/ni.2131 · Cited by 1,286
Mjösberg, J. M., Trifari, S., Crellin, N. K., Peters, C. P., van Drunen, C. M., Piet, B., Fokkens, W. J., Cupedo, T., & Spits, H. (2011) · Nature Immunology · doi:10.1038/ni.2104 · Cited by 1,166
Systemically dispersed innate IL-13–expressing cells in type 2 immunity
Price, A. E., Liang, H.-E., Sullivan, B. M., Reinhardt, R. L., Eisley, C. J., Erle, D. J., & Locksley, R. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003988107 · Cited by 1,134
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Items 501–504 of 504
The IL-33-ILC2 axis: a key regulator of type 2 immunity in respiratory disease
Zhu, Y., Zhang, Y., & Cheng, R. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1891857
Andersson, L. K., Bollmann, M., Lastowska, A., Haupt, I., Wagener, L., Nguyen, A., Svensson, J., Johansson, L., & Svensson, M. N. D. (2026) · Journal of Immunology Research · doi:10.1155/jimr/7688318
LÜCKMANN, L. F., Dal-Pizzol, H. R., Lückmann, L. M., Salini, D., Hasckel, B. C., Minati, M., Kluwe‐Schiavon, B., & Tatiana, B. (2026) · Immunology · doi:10.1111/imm.70202
Metadata
- Authors
- Mchedlidze, T., Waldner, M., Zopf, S., Walker, J., Rankin, A. L., Schuchmann, M., Voehringer, D., McKenzie, A. N. J., Neurath, M. F., Pflanz, S., & Wirtz, S.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- MRC Laboratory of Molecular Biology (GB)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Wirtz, Stefan
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 39
- Issue
- 2
- Pages
- 357-371
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4172965
- OpenAlex
- W1997883939
- Cited by
- 502
- References
- 54
- Citations by year
- 2026: 13 · 2025: 33 · 2024: 30 · 2023: 33 · 2022: 35 · 2021: 37 · 2020: 46 · 2019: 43 · 2018: 48 · 2017: 50 · 2016: 47 · 2015: 47 · 2014: 35 · 2013: 4
- FWCI
- 24.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- IL-33, liver fibrosis, innate lymphoid cells, ILC2, IL-13, STAT6, hepatic stellate cells, extracellular matrix remodeling, liver inflammation, chronic liver disease
- MeSH terms
- Interleukin-33, Animals, Cells, Cultured, Inflammation, Interleukins, Liver, Liver Cirrhosis, Lymphocyte Activation, Lymphocytes, Mice, Inbred BALB C, Mice, Inbred C57BL, Signal Transduction, Mice, Knockout, Interleukin-13, Adoptive Transfer, Cell Proliferation, STAT6 Transcription Factor, Mice, Receptors, Interleukin-4, Type II, Hepatic Stellate Cells
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