Interleukin-22 protects intestinal stem cells against genotoxic stress

Gronke, Konrad; Hernández, Pedro P.; Zimmermann, Jakob; Klose, Christoph S. N.; Kofoed-Branzk, Michael; Guendel, Fabian; Witkowski, Mario; Tizian, Caroline; Amann, Lukas; Schumacher, Fabian; Glatt, Hansruedi; Triantafyllopoulou, Antigoni; Diefenbach, Andreas

doi:10.1038/s41586-019-0899-7

Cited by 290 publications

(263 citation statements)

References 48 publications

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“…IL‐22‐deficient crypts lost the control of apoptosis through the DNA damage response. This dysregulation triggered the formation of colon cancer upon AOM treatment, highlighting the importance of IL‐22 in colon cancer carcinogenesis . In the same study, they could also demonstrate that dietary‐derived AhR ligands directly induce genotoxic stress in intestinal epithelial cells, while at the same time promoting IL‐22 production in ILC3s, which in return switches on the DNA damage response in intestinal epithelial cells.…”

Section: Microbiota − Ilcs Cancer and Agingmentioning

confidence: 72%

“…This dysregulation triggered the formation of colon cancer upon AOM treatment, highlighting the importance of IL-22 in colon cancer carcinogenesis. 46 In the same study, they could also demonstrate that dietary-derived AhR ligands directly induce genotoxic stress in intestinal epithelial cells, while at the same time promoting IL-22 production in ILC3s, which in return switches on the DNA damage response in intestinal epithelial cells. These studies further underline that ILC3s are key players in homeostatic but also in inflammatory conditions at the interface between the environment and the body.…”

Section: Microbiota à Ilcs Cancer and Agingmentioning

confidence: 87%

“…Recently, Gronke et al . demonstrated that ILC3‐derived IL‐22 induces the DNA damage response in intestinal epithelial cells, protecting the epithelial layer from exogenous genotoxic stress, thus limiting tumorigenesis . The production of IL‐22 by both CCR6 − and CCR6 + ILC3s is stimulated by commensal microbiota as shown by the use of GF and antibiotic‐treated mice .…”

Section: Microbiota and Ilc Interactions During Steady‐state In Adultmentioning

confidence: 99%

“…45 Recently, Gronke et al demonstrated that ILC3-derived IL-22 induces the DNA damage response in intestinal epithelial cells, protecting the epithelial layer from exogenous genotoxic stress, thus limiting tumorigenesis. 46 The production of IL-22 by both CCR6 À and CCR6 + ILC3s is stimulated by commensal microbiota as shown by the use of GF and antibiotic-treated mice. 29 ILC3-derived IL-22 induces the expression of various other factors in the epithelium, including tight and gap junction proteins, mucins, and cytokine receptors that contribute to the homeostasis and barrier function of the epithelium (for review, see Ref.…”

Section: Microbiota and Ilc Interactions During Steadystate In Adulthoodmentioning

confidence: 99%

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The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life

Ganal‐Vonarburg

Duerr

2019

Immunology

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Summary Immunity is shaped by commensal microbiota. From early life onwards, microbes colonize mucosal surfaces of the body and thereby trigger the establishment of immune homeostasis and defense mechanisms. Recent evidence reveals that the family of innate lymphoid cells (ILCs), which are mainly located in mucosal tissues, are essential in the maintenance of barrier functions as well as in the initiation of an appropriate immune response upon pathogenic infection. In this review, we summarize recent insights on the functional interaction of microbiota and ILCs at steady‐state and throughout life. Furthermore, we will discuss the interplay of ILCs and the microbiota in mucosal infections focusing on intestinal immunity.

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Section: Microbiota − Ilcs Cancer and Agingmentioning

confidence: 72%

Section: Microbiota à Ilcs Cancer and Agingmentioning

confidence: 87%

Section: Microbiota and Ilc Interactions During Steady‐state In Adultmentioning

confidence: 99%

Section: Microbiota and Ilc Interactions During Steadystate In Adulthoodmentioning

confidence: 99%

See 2 more Smart Citations

The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life

Ganal‐Vonarburg

Duerr

2019

Immunology

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“…IL-22 is also required for activation of the DNA damage response in the intestinal epithelium. In a series of elegant experiments, Gronke et al (2019) demonstrated that selective removal of IL-22RA1 from IECs leads to suppression of apoptosis triggered by DNA damage, and, as a consequence, increased tumor formation in an inflammation-driven tumor model. A group of phytochemicals called glucosinolates, which are abundant in cruciferous vegetables, can give rise to metabolites with DNA-damaging potential yet are also known to activate aryl hydrocarbon receptor signaling, leading to IL-22 production.…”

Section: Role Of Il-22 In Intestinal Stem Cells (Iscs) and Epithelial Regenerationmentioning

confidence: 99%

The role of IL-22 in intestinal health and disease

Keir¹,

Yi²,

Lu³

et al. 2020

Journal of Experimental Medicine

289

160

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The cytokine interleukin-22 (IL-22) is a critical regulator of epithelial homeostasis. It has been implicated in multiple aspects of epithelial barrier function, including regulation of epithelial cell growth and permeability, production of mucus and antimicrobial proteins (AMPs), and complement production. In this review, we focus specifically on the role of IL-22 in the intestinal epithelium. We summarize recent advances in our understanding of how IL-22 regulates homeostasis and host defense, and we discuss the IL-22 pathway as a therapeutic target in diseases of the intestine, including inflammatory bowel disease (IBD), graft-versus-host disease (GVHD), and cancer.

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Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer

Zhang

et al. 2023

Advanced Science

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Colorectal cancer (CRC) is the most common cancer of the digestive system with high mortality and morbidity rates. Gut microbiota is found in the intestines, especially the colorectum, and has structured crosstalk interactions with the host that affect several physiological processes. The gut microbiota include CRC‐promoting bacterial species, such as Fusobacterium nucleatum, Escherichia coli, and Bacteroides fragilis, and CRC‐protecting bacterial species, such as Clostridium butyricum, Streptococcus thermophilus, and Lacticaseibacillus paracasei, which along with other microorganisms, such as viruses and fungi, play critical roles in the development of CRC. Different bacterial features are identified in patients with early‐onset CRC, combined with different patterns between fecal and intratumoral microbiota. The gut microbiota may be beneficial in the diagnosis and treatment of CRC; some bacteria may serve as biomarkers while others as regulators of chemotherapy and immunotherapy. Furthermore, metabolites produced by the gut microbiota play essential roles in the crosstalk with CRC cells. Harmful metabolites include some primary bile acids and short‐chain fatty acids, whereas others, including ursodeoxycholic acid and butyrate, are beneficial and impede tumor development and progression. This review focuses on the gut microbiota and its metabolites, and their potential roles in the development, diagnosis, and treatment of CRC.

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Interleukin-22 protects intestinal stem cells against genotoxic stress

Cited by 290 publications

References 48 publications

The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life

The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life

The role of IL-22 in intestinal health and disease

Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer

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