IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine
Standard
IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. / Huber, Samuel; Gagliani, Nicola; Zenewicz, Lauren A; Huber, Francis J; Bosurgi, Lidia; Hu, Bo; Hedl, Matija; Zhang, Wei; O'Connor, William; Murphy, Andrew J; Valenzuela, David M; Yancopoulos, George D; Booth, Carmen J; Cho, Judy H; Ouyang, Wenjun; Abraham, Clara; Flavell, Richard A.
in: NATURE, Jahrgang 491, Nr. 7423, 7423, 08.11.2012, S. 259-263.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine
AU - Huber, Samuel
AU - Gagliani, Nicola
AU - Zenewicz, Lauren A
AU - Huber, Francis J
AU - Bosurgi, Lidia
AU - Hu, Bo
AU - Hedl, Matija
AU - Zhang, Wei
AU - O'Connor, William
AU - Murphy, Andrew J
AU - Valenzuela, David M
AU - Yancopoulos, George D
AU - Booth, Carmen J
AU - Cho, Judy H
AU - Ouyang, Wenjun
AU - Abraham, Clara
AU - Flavell, Richard A
PY - 2012/11/8
Y1 - 2012/11/8
N2 - 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.
AB - 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.
KW - Animals
KW - Time Factors
KW - Disease Models, Animal
KW - Mice
KW - Mice, Knockout
KW - Down-Regulation
KW - Cell Transformation, Neoplastic
KW - Colitis/complications/metabolism/pathology
KW - Colon/metabolism/pathology
KW - Colonic Neoplasms/complications/metabolism/pathology
KW - Epithelial Cells/metabolism/pathology
KW - Genes, APC
KW - Inflammasomes/metabolism
KW - Interleukin-18/metabolism
KW - Interleukins/deficiency/genetics/metabolism
KW - Intestines/metabolism/pathology
KW - Receptors, Interleukin/deficiency/genetics/metabolism
KW - Weight Loss
KW - Animals
KW - Time Factors
KW - Disease Models, Animal
KW - Mice
KW - Mice, Knockout
KW - Down-Regulation
KW - Cell Transformation, Neoplastic
KW - Colitis/complications/metabolism/pathology
KW - Colon/metabolism/pathology
KW - Colonic Neoplasms/complications/metabolism/pathology
KW - Epithelial Cells/metabolism/pathology
KW - Genes, APC
KW - Inflammasomes/metabolism
KW - Interleukin-18/metabolism
KW - Interleukins/deficiency/genetics/metabolism
KW - Intestines/metabolism/pathology
KW - Receptors, Interleukin/deficiency/genetics/metabolism
KW - Weight Loss
U2 - 10.1038/nature11535
DO - 10.1038/nature11535
M3 - SCORING: Journal article
C2 - 23075849
VL - 491
SP - 259
EP - 263
JO - NATURE
JF - NATURE
SN - 0028-0836
IS - 7423
M1 - 7423
ER -
