IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine
By S. Huber, N. Gagliani, Lauren A. Zenewicz, Francis J. Huber, L. Bosurgi, Bo Hu, M. Hedl, William O'Connor, A. Murphy, D. Valenzuela and 6 more. Nature, 2012
719 citations recorded by the source corpus.
Chronic mucosal inflammation and tissue damage predisposes patients to the development of colorectal cancer. This association could be explained by the hypothesis that the same factors and pathways important for wound healing also promote tumorigenesis. A sensor of tissue damage should induce these factors to promote tissue repair and regulate their action to prevent development of cancer. Interleukin 22 (IL-22), a cytokine of the IL-10 superfamily, has an important role in colonic epithelial cell repair, and its levels are increased in the blood and intestine of inflammatory bowel disease patients. This cytokine can be neutralized by the soluble IL-22 receptor, known as the IL-22 binding protein (IL-22BP, also known as IL22RA2); however, the significance of endogenous IL-22BP in vivo and the pathways that regulate this receptor are unknown. Here we describe that IL-22BP has a crucial role in controlling tumorigenesis and epithelial cell proliferation in the colon. IL-22BP is highly expressed by dendritic cells in the colon in steady-state conditions. Sensing of intestinal tissue damage via the NLRP3 or NLRP6 inflammasomes led to an IL-18-dependent downregulation of IL-22BP, thereby increasing the ratio of IL-22/IL-22BP. IL-22, which is induced during intestinal tissue damage, exerted protective properties during the peak of damage, but promoted tumour development if uncontrolled during the recovery phase. Thus, the IL-22–IL-22BP axis critically regulates intestinal tissue repair and tumorigenesis in the colon.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/6f5e7ebf54492c8bb13c229fff6cada6a8f9fab0
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Citations in the corpus
- Interleukin-22: immunobiology and pathology (2015, background): “However, in later periods after IL-22 has been induced, levels of IL-22BP can increase indicating a regulatory role after the initial early effects of IL-22 (217, 220, 221).”
- Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “Indeed, NF-κB dependent cytokines confer unique and non-redundant roles in tumor growth as their genetic or pharmacological inactivation reduces tumor growth acting through activation of other oncogenic pathways in epithelial and cancer cells, including STAT3, ERK, JUN and receptor Tyr-kinases (RTK)”
- The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation (2016, background): “Toll/Interleukin receptor domain-containing adapter-inducing interferon β (TRIF) is a caspase-1 substrate, such that caspase-1 activation reduces TRIF-dependent type I IFN–mediated autophagy (Jabir et al., 2014).”
- Innate Lymphoid Cells: 10 Years On. (2018, positive): “While constitutive absence of IL-22 enhances inflammationdriven colorectal cancer (Huber et al., 2012), the proliferationpromoting effect of IL-22 on epithelial cells can also sustain the progression of colon cancer (Kirchberger et al.”
- Mechanisms and consequences of intestinal dysbiosis (2017, background): “In contrast, IL-18 also down-regulates IL-22-binding protein, which enables IL-22 to induce intestinal tissue repair and expression of antimicrobial peptides [126, 127].”
- Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. (2019, background): “However, reparative effects on IEC can render IL-22 a pathogenic player in intestinal tumorigenesis if uncontrolled (Huber et al., 2012; Kirchberger et al., 2013), which may eventually limit its clinical utility.”