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Citations to this article

IL-33 regulates the IgA-microbiota axis to restrain IL-1α–dependent colitis and tumorigenesis
Ankit Malik, … , Peter Vogel, Thirumala-Devi Kanneganti
Ankit Malik, … , Peter Vogel, Thirumala-Devi Kanneganti
Published October 24, 2016
Citation Information: J Clin Invest. 2016;126(12):4469-4481. https://doi.org/10.1172/JCI88625.
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Research Article Immunology Article has an altmetric score of 5

IL-33 regulates the IgA-microbiota axis to restrain IL-1α–dependent colitis and tumorigenesis

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Abstract

Inflammatory bowel diseases (IBD) affect over 5 million individuals in the industrialized world, with an increasing incidence rate worldwide. IBD also predisposes affected individuals to development of colorectal cancer, which is a leading cause of cancer-related deaths in adults. Mutations in genes encoding molecules in the IL-33 signaling pathway are associated with colitis and colitis-associated cancer (CAC), but how IL-33 modulates gut homeostasis is unclear. Here, we have shown that Il33-deficient mice are highly susceptible to colitis and CAC. Mechanistically, we observed that IL-33 promoted IgA production from B cells, which is important for maintaining microbial homeostasis in the intestine. Il33-deficient mice developed a dysbiotic microbiota that was characterized by increased levels of mucolytic and colitogenic bacteria. In response to chemically induced colitis, this microbial landscape promoted the release of IL-1α, which acted as a critical driver of colitis and CAC. Consequently, reconstitution of symbiotic microbiota or IL-1α ablation markedly ameliorated colitis susceptibility in Il33-deficient animals. Our results demonstrate that IL-33 promotes IgA production to maintain gut microbial homoeostasis and restrain IL-1α–dependent colitis and CAC. This study therefore highlights modulation of IL-33, IgA, IL-1α, and the microbiota as a potential therapeutic approach in the treatment of IBD and CAC.

Authors

Ankit Malik, Deepika Sharma, Qifan Zhu, Rajendra Karki, Clifford S. Guy, Peter Vogel, Thirumala-Devi Kanneganti

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 Total
Citations: 4 11 10 16 15 15 19 14 11 115
Citation information
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Citations to this article in year 2018 (14)

Title and authors Publication Year
Interleukin-33 and ST2 Signaling in Tumor Microenvironment
J Hong, S Kim, PC Lin
Journal of Interferon & Cytokine Research 2018
Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles
H Kayama, M Kohyama, D Okuzaki, D Motooka, S Barman, R Okumura, M Muneta, K Hoshino, I Sasaki, W Ise, H Matsuno, J Nishimura, T Kurosaki, S Nakamura, H Arase, T Kaisho, K Takeda
Proceedings of the National Academy of Sciences 2018
IL-33 facilitates proliferation of colorectal cancer dependent on COX2/PGE2
Y Li, J Shi, S Qi, J Zhang, D Peng, Z Chen, G Wang, Z Wang, L Wang
Journal of Experimental & Clinical Cancer Research 2018
IL-33/ST2 Axis in Organ Fibrosis
OS Kotsiou, KI Gourgoulianis, SG Zarogiannis
Frontiers in immunology 2018
Mast cells are essential intermediaries in regulating IL-33/ST2 signaling for an immune network favorable to mucosal healing in experimentally inflamed colons
Z He, J Song, J Hua, M Yang, Y Ma, T Yu, J Feng, B Liu, X Wang, Y Li, J Li
Cell Death and Disease 2018
Caspase-1 from Human Myeloid-Derived Suppressor Cells Can Promote T Cell–Independent Tumor Proliferation
Q Zeng, J Fu, M Korrer, M Gorbounov, PJ Murray, D Pardoll, DL Masica, YJ Kim
Cancer immunology research 2018
Do Alarmins Have a Potential Role in Autism Spectrum Disorders Pathogenesis and Progression?
ED Salvo, M Casciaro, S Quartuccio, L Genovese, S Gangemi
Biomolecules 2018
The Pleiotropic Immunomodulatory Functions of IL-33 and Its Implications in Tumor Immunity
C Afferni, C Buccione, S Andreone, MR Galdiero, G Varricchi, G Marone, F Mattei, G Schiavoni
Frontiers in immunology 2018
Interleukin 1α-Deficient Mice Have an Altered Gut Microbiota Leading to Protection from Dextran Sodium Sulfate-Induced Colitis
M Nunberg, N Werbner, H Neuman, M Bersudsky, A Braiman, M Ben-Shoshan, MB Izhak, Y Louzoun, RN Apte, E Voronov, O Koren, KL Whiteson
mSystems 2018
Can We Target Endogenous Anti-inflammatory Responses as a Therapeutic Strategy for Inflammatory Bowel Disease?
RJ Porter, C Andrews, DP Brice, SK Durum, MH McLean
Inflammatory Bowel Diseases 2018
Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions
M Mamantopoulos, F Ronchi, KD McCoy, A Wullaert
Gut microbes 2018
Lower expression level of IL-33 is associated with poor prognosis of pulmonary adenocarcinoma
M Yang, Y Feng, C Yue, B Xu, L Chen, J Jiang, B Lu, Y Zhu, A Ahmad
PloS one 2018
Irreversible effects of trichloroethylene on the gut microbial community and gut-associated immune responses in autoimmune-prone mice: TEC causes persistent changes in gut microbiome and immune status
S Khare, K Gokulan, K Williams, S Bai, KM Gilbert, SJ Blossom
Journal of applied toxicology : JAT 2018
SYK-CARD9 Signaling Axis Promotes Gut Fungi-Mediated Inflammasome Activation to Restrict Colitis and Colon Cancer
A Malik, D Sharma, RK Malireddi, CS Guy, TC Chang, SR Olsen, G Neale, P Vogel, TD Kanneganti
Immunity 2018

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