Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer

Dmitrieva-Posocco, Oxana; Dzutsev, Amiran; Posocco, David; Hou, Vivianty; Yuan, Wuxing; Thovarai, Vishal; Mufazalov, Ilgiz A.; Gunzer, Matthias; Shilovskiy, Igor; Khaitov, Musa; Trinchieri, Giorgio; Waisman, Ari; Grivennikov, Sergei I.

doi:10.1016/j.immuni.2018.11.015

Cited by 136 publications

(104 citation statements)

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“…The role of IL-1 in colorectal cancer was recently dissected by using cell-type-specific IL-1R1-deficient mice. This study showed that IL-1 had pro-tumor effects by promoting Th17-mediated inflammation through IL-17 and IL-22, and epithelial-cell-autonomous mechanisms, whereas IL-1 had tumor-suppressive effects by promoting neutrophilmediated control of bacterial invasion (Dmitrieva-Posocco et al, 2019).…”

Section: Il-1 Family Members In Maintenance Of Homeostasis and Gastromentioning

confidence: 78%

Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity

et al. 2019

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Forty years after its naming, interleukin-1 (IL-1) is experiencing a renaissance brought on by the growing understanding of its context-dependent roles and advances in the clinic. Recent studies have identified important roles for members of the IL-1 family-IL-18, IL-33, IL-36, IL-37, and IL-38-in inflammation and immunity. Here, we review the complex functions of IL-1 family members in the orchestration of innate and adaptive immune responses and their diversity and plasticity. We discuss the varied roles of IL-1 family members in immune homeostasis and their contribution to pathologies, including autoimmunity and autoinflammation, dysmetabolism, cardiovascular disorders, and cancer. The trans-disease therapeutic activity of anti-IL-1 strategies argues for immunity and inflammation as a metanarrative of modern medicine. 2018). This suggests the evolutive relevance of balanced responses in the IL-1 system. Interleukin-1 receptor family members (ILRs) are present in all vertebrates and originated through ancestral gene duplication 25 S IN CE 1 99 4 T W T EN

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Section: Il-1 Family Members In Maintenance Of Homeostasis and Gastromentioning

confidence: 78%

Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity

et al. 2019

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“…Indeed, a recent study has elegantly demonstrated opposing roles of cell-type specific IL-1R signaling in CRC. The protumorigenic roles of IL-1R in epithelial and T-cells are counteracted by its effects on myeloid cells, particularly neutrophils, where IL-1R signaling contributes to deter tumorinfiltrating bacteria and dampen CRC promoting inflammation 99 . A similar approach has been studied for the role of ASC in skin tumorigenesis, where inflammasome activation driven by ASC in myeloid cells favors epithelial skin tumorigenesis, whereas ASC in keratinocytes serves to limit proliferation, possibly through p53 activation in an inflammasome-independent manner 100 .…”

Section: Protection In Colorectal Cancermentioning

confidence: 99%

Diverging inflammasome signals in tumorigenesis and potential targeting

2019

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Inflammasomes are molecular platforms that assemble upon sensing various intracellular stimuli. Inflammasome assembly leads to activation of caspase-1, thereby promoting the secretion of bioactive interleukin-1β and interleukin-18 and inducing an inflammatory cell death called pyroptosis. Effectors of the inflammasome efficiently drive an immune response, primarily providing protection against microbial infections and mediating control over sterile insults. However, aberrant inflammasome signaling is associated with pathogenesis of inflammatory and metabolic diseases, neurodegeneration, and malignancies. Chronic inflammation perpetuated by inflammasome activation plays a central role in all stages of tumorigenesis, including immunosuppression, proliferation, angiogenesis, and metastasis. Conversely, inflammasome signaling also contributes to tumor suppression by maintaining intestinal barrier integrity, which portrays the diverse roles of inflammasomes in tumorigenesis. Studies have underscored the significance of environmental factors, such as diet and gut microbiota [G] in inflammasome signaling, which in turn influences tumorigenesis. In this review, we deliver an overview of the interplay between inflammasomes and tumorigenesis and discuss their potential as a therapeutic target. ToC blurb Inflammasome signaling in myeloid cells largely protects against microbial infections. Aberrant inflammasome signaling promotes chronic inflammation, which contributes to tumorigenesis. This Review presents an overview of the diverging roles of inflammasomes in cancer and discuss its targeting potential in anti-cancer therapy.

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“…On the flip side, IL-22 has been shown to promote tumor growth in some models (Dmitrieva-Posocco et al, 2019; Kirchberger et al, 2013). This is consistent with the fact that IL-22 is a potent activator of STAT3 in epithelial cells, and STAT3 is required for the development of colitis-associated cancer (Bollrath et al, 2009; Grivennikov et al, 2009).…”

Section: Cancermentioning

confidence: 99%

The role of IL-22 in intestinal health and disease

Keir¹,

Yi²,

Lu³

et al. 2020

Journal of Experimental Medicine

291

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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Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer

Cited by 136 publications

References 50 publications

Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity

Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity

Diverging inflammasome signals in tumorigenesis and potential targeting

The role of IL-22 in intestinal health and disease

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