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

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

doi:10.1172/jci88625

Cited by 144 publications

(151 citation statements)

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“…Indeed, studies investigating intestinal epithelial-specific TLR5 deficiency or full-body ablation of Card9 or IL-33 showed that weaning these genetic mouse models and their WT littermates in separate cages resulted in differential gut microbiota communities after 4–6 weeks of separation. 36-38 Together, these several mouse genetic studies show that analyzing separately housed littermates is a well-controlled and valid approach for dissecting host genetic effects on intestinal ecosystems.…”

Section: Resultsmentioning

confidence: 99%

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions

et al. 2018

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Several human diseases are thought to evolve due to a combination of host genetic mutations and environmental factors that include alterations in intestinal microbiota composition termed dysbiosis. Although in some cases, host genetics may shape the gut microbiota and enable it to provoke disease, experimentally disentangling cause and consequence in such host-microbe interactions requires strict control over non-genetic confounding factors. Mouse genetic studies previously proposed Nlrp6/ASC inflammasomes as innate immunity regulators of the intestinal ecosystem. In contrast, using littermate-controlled experimental setups, we recently showed that Nlrp6/ASC inflammasomes do not alter the gut microbiota composition. Our analyses indicated that maternal inheritance and long-term separate housing are non-genetic confounders that preclude the use of non-littermate mice when analyzing host genetic effects on intestinal ecology. Here, we summarize and discuss our gut microbiota analyses in inflammasome-deficient mice for illustrating the importance of littermate experimental design in studying host-microbiota interactions.

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Section: Resultsmentioning

confidence: 99%

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions

et al. 2018

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“…In the gut, the microbiome has been established to be a significant mediator of metabolism and local inflammation [81–85]. A recent study demonstrated that IL-33 is an important regulator of the components of the microbiome [86]. Mice deficient in IL-33 are dysbiotic, or have a higher concentration of pro-inflammatory bacteria that comprise their microbiome compared to their wild-type (WT) controls [86].…”

Section: Il-33: An Alarmin In the Intestinementioning

confidence: 99%

“…A recent study demonstrated that IL-33 is an important regulator of the components of the microbiome [86]. Mice deficient in IL-33 are dysbiotic, or have a higher concentration of pro-inflammatory bacteria that comprise their microbiome compared to their wild-type (WT) controls [86]. Specifically, IL-33-deficient mice have more segmented filamentous bacteria that have also been found in higher concentrations in mouse models of inflammatory bowel disease as well as increased Akkermansia muciniphila , which can degrade mucus [86–88].…”

Section: Il-33: An Alarmin In the Intestinementioning

confidence: 99%

“…Mice deficient in IL-33 are dysbiotic, or have a higher concentration of pro-inflammatory bacteria that comprise their microbiome compared to their wild-type (WT) controls [86]. Specifically, IL-33-deficient mice have more segmented filamentous bacteria that have also been found in higher concentrations in mouse models of inflammatory bowel disease as well as increased Akkermansia muciniphila , which can degrade mucus [86–88]. Consequently, this dysbiosis promoted release of IL-1α, which drives colitis and even tumor formation [86].…”

Section: Il-33: An Alarmin In the Intestinementioning

confidence: 99%

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IL-33 and the intestine: The good, the bad, and the inflammatory

et al. 2017

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Interleukin-33 (IL-33) is a member of the IL-1 cytokine family that has been widely studied since its discovery in 2005 for its dichotomous functions in homeostasis and inflammation. IL-33, along with its receptor suppression of tumorigenicity 2 (ST2), has been shown to modulate both the innate and adaptive immune system. Originally, the IL-33/ST2 signaling axis was studied in the context of inducing type 2 immune responses with the expression of ST2 by T helper 2 (TH2) cells. However, the role of IL-33 is not limited to TH2 responses. Rather, IL-33 is a potent activator of TH1 cells, group 2 innate lymphoid cells (ILC2s), regulatory T (Treg) cells, and CD8+ T cells. The intestine is uniquely important in this discussion, as the intestinal epithelium is distinctively positioned to interact with both pathogens and the immune cells housed in the mucosa. In the intestine, IL-33 is expressed by the pericryptal fibroblasts and its expression is increased particularly in disease states. Moreover, IL-33/ST2 signaling aberrancy is implicated in the pathogenesis of inflammatory bowel disease (IBD). Accordingly, for this review, we will focus on the role of IL-33 in the regulation of intestinal immunity, involvement in intestinal disease, and implication in potential therapeutics.

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“…The NLRP3 inflammasome complex, in some colorectal carcinoma models, can confer an anticarcinogenic effect (30)(31)(32)(33)(34). However, other murine models in gastric cancers, B16F10 melanoma, colitis-associated colon cancer, and T-ALL have variously shown opposing pro-tumorigenic activities of inflammasome cytokines (35,36). Chemotherapy can further confound the picture to activate the NLRP3 inflammasome to promote tumor growth rate (37).…”

mentioning

confidence: 99%

Caspase-1 from Human Myeloid-Derived Suppressor Cells Can Promote T Cell–Independent Tumor Proliferation

Zeng

Korrer

et al. 2018

Cancer Immunology Research

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

Cited by 144 publications

References 63 publications

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions

IL-33 and the intestine: The good, the bad, and the inflammatory

Caspase-1 from Human Myeloid-Derived Suppressor Cells Can Promote T Cell–Independent Tumor Proliferation

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