Innate lymphoid cells regulate intestinal epithelial cell glycosylation

Goto, Yoshiyuki; Obata, Takashi; Kunisawa, Jun; Sato, Shintaro; Ivanov, Ivaylo I.; Lamichhane, Aayam; Takeyama, Natsumi; Kamioka, Mariko; Sakamoto, Mitsuo; Matsuki, Takahiro; Setoyama, Hiromi; Imaoka, Akemi; Uematsu, Satoshi; Akira, Shizuo; Domino, Steven E.; Kulig, Paulina; Becher, Burkhard; Renauld, Jean‐Christophe; Sasakawa, Chihiro; Umesaki, Yoshinori; Benno, Yoshimi; Kiyono, Hiroshi

doi:10.1126/science.1254009

Cited by 465 publications

(463 citation statements)

References 56 publications

(116 reference statements)

Supporting

Mentioning

420

Contrasting

Unclassified

Order By: Relevance

“…S7). It will be interesting to dissect the contributions of individual members of the microbiota such as segmented filamentous bacteria (18) and systemic signals acting through TLR (19) in TIR-dependent regulation of small intestinal fucosylation. Furthermore, we found that many UDP glucuronosyltransferases (Ugt) members show aberrant regulation in the colon in the absence of TIR signaling ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Analysis of gene–environment interactions in postnatal development of the mammalian intestine

Rakoff-Nahoum

Kong

Kleinstein

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Unlike mammalian embryogenesis, which takes place in the relatively predictable and stable environment of the uterus, postnatal development can be affected by a multitude of highly variable environmental factors, including diet, exposure to noxious substances, and microorganisms. Microbial colonization of the intestine is thought to play a particularly important role in postnatal development of the gastrointestinal, metabolic, and immune systems. Major changes in environmental exposure occur right after birth, upon weaning, and during pubertal maturation into adulthood. These transitions include dramatic changes in intestinal contents and require appropriate adaptations to meet changes in functional demands. Here, we attempt to both characterize and provide mechanistic insights into postnatal intestinal ontogeny. We investigated changes in global intestinal gene expression through postnatal developmental transitions. We report profound alterations in small and large intestinal transcriptional programs that accompany both weaning and puberty in WT mice. Using myeloid differentiation factor 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) double knockout littermates, we define the role of toll-like receptors (TLRs) and interleukin (IL)-1 receptor family member signaling in postnatal gene expression programs and select ontogeny-specific phenotypes, such as vascular and smooth muscle development and neonatal epithelial and mast cell homeostasis. Metaanalysis of the effect of the microbiota on intestinal gene expression allowed for mechanistic classification of developmentally regulated genes by TLR/IL-1R (TIR) signaling and/or indigenous microbes. We find that practically every aspect of intestinal physiology is affected by postnatal transitions. Developmental timing, microbial colonization, and TIR signaling seem to play distinct and specific roles in regulation of gene-expression programs throughout postnatal development.

show abstract

Section: Resultsmentioning

confidence: 99%

Analysis of gene–environment interactions in postnatal development of the mammalian intestine

Rakoff-Nahoum

Kong

Kleinstein

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…IL-22 has been shown to play a critical role in mucosal immunity at barrier surfaces, including the gastrointestinal tract and in the lung (24). In the gut, IL-22 regulates the expression of antimicrobial proteins, such as Reg3␥ (25), and can also increase fucosylation through the upregulation of Fut2, resulting in enhanced resistance to pathogens (26)(27)(28). IL-22 can also activate STAT1 and increase antiviral immunity in the gut (23).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Role of Interleukin 22 in Experimental Intra-abdominal Klebsiella pneumoniae Infection in Mice

et al. 2016

View full text Add to dashboard Cite

Hep؊/؊ ) and Stat3 knockout (Stat3 Hep؊/؊ ) mice were generated and subjected to intra-abdominal infection with Klebsiella pneumoniae, which results in liver injury and necrosis. We found that overexpression of IL-22 or therapeutic administration of recombinant IL-22 (rIL-22), given 2 h postinfection, significantly reduced the bacterial burden in both the liver and spleen. The antimicrobial activity of rIL-22 required hepatic Il22Ra1 and Stat3. Serum from rIL-22-treated mice showed potent bacteriostatic activity against K. pneumoniae, which was dependent on lipocalin 2 (LCN2). However, in vivo, rIL-22-induced antimicrobial activity was only partially reduced in LCN2-deficient mice. We found that rIL-22 also induced serum amyloid A2 (SAA2) and that SAA2 had anti-K. pneumoniae bactericidal activity in vitro. These results demonstrate that IL-22, through IL-22Ra1 and STAT3 singling, can induce intrinsic antimicrobial activity in the liver, which is due in part to LCN2 and SAA2. Therefore, IL-22 may be a useful adjunct in treating hepatic and intra-abdominal infections.

show abstract

“…Further studies specifically depleting LTi‐like ILC3 are needed to determine whether these findings merely reflect redundancy among IL‐22‐producing ILC3 or subset‐specific roles in the regulation of commensal bacterial species. ILC3‐derived IL‐22 also results in fucosylation of intestinal epithelial cell‐associated carbohydrate chains following colonization of the intestinal tract by commensal bacteria 85, 86, 87. Whereas, certain species of mutualistic bacteria possess the necessary machinery to use carbohydrate fucose as an energy source, many pathogenic bacteria lack this ability and are outcompeted for energy sources.…”

Section: Ilc3 Functions Under Homeostatic Conditionsmentioning

confidence: 99%

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

2017

View full text Add to dashboard Cite

SummaryGroup 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid‐related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR + ILC3 and LTi‐like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever‐expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation – with a focus on comparing and contrasting the relative contributions of ILC3 subsets.

show abstract

Innate lymphoid cells regulate intestinal epithelial cell glycosylation

Cited by 465 publications

References 56 publications

Analysis of gene–environment interactions in postnatal development of the mammalian intestine

Analysis of gene–environment interactions in postnatal development of the mammalian intestine

Therapeutic Role of Interleukin 22 in Experimental Intra-abdominal Klebsiella pneumoniae Infection in Mice

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

Contact Info

Product

Resources

About