Microbial Flora Drives Interleukin 22 Production in Intestinal NKp46+ Cells that Provide Innate Mucosal Immune Defense

Satoh-Takayama, Naoko; Vosshenrich, Christian A. J.; Lesjean-Pottier, Sarah; Sawa, Shinichiro; Lochner, Matthias; Rattis, Frédérique Marie; Mention, Jean Jacques; Thiam, Kader; Cerf‐Bensussan, Nadine; Mandelboim, Ofer; Eberl, Gérard; Santo, James P. Di

doi:10.1016/j.immuni.2008.11.001

Cited by 994 publications

(1,244 citation statements)

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“…Expression of ROR γ t is essential for the development and maturation of all members of the ILC3 family, including fetal LTi, adult LTi‐like ILC3 and NKp46 + ILC3 24, 25, 26, 27. ROR γ t‐expressing progenitors are present in the fetal liver of mice 14.…”

Section: Group 3 Innate Lymphoid Cell Developmentmentioning

confidence: 99%

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

2017

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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.

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Section: Group 3 Innate Lymphoid Cell Developmentmentioning

confidence: 99%

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

2017

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“…Innate lymphoid cells (ILC) are effector cells contributing to the early immune responses against microbes 1, stimulating tissue regeneration 2 and strengthening the epithelial barrier at mucosal surfaces 3. A detailed description of the tissue‐specific functions of the human ILC subsets have recently been provided elsewhere 4.…”

Section: Development and Classification Of Ilc Subsetsmentioning

confidence: 99%

“…Importantly, the healthy human intestine hosts dominantly NCR + ILC3, which have been shown to be essential in maintaining gut homeostasis 1. The signature cytokine of NCR + ILC3 is IL‐22, a cytokine belonging to the IL‐10 cytokine family.…”

Section: Ilc Subsetsmentioning

confidence: 99%

“…Exceptionally among cytokines, IL‐22 does not target immune cells, but stromal cells and epithelial cells at physical barriers, such as skin, gut, and liver 27. Mouse studies established a crucial role for IL‐22 in gut homeostasis, since ILC3‐derived IL‐22 protected against Citrobacter rodentium –induced colitis 1. Furthermore, IL‐22‐producing ILC3 in the gut were found to control anatomical containment of commensal bacteria, thereby protecting against intestinal inflammation 28.…”

Section: Ilc Subsetsmentioning

confidence: 99%

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Innate Lymphoid Cells in Graft-Versus-Host Disease

Kónya

Mjösberg

2015

American Journal of Transplantation

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Innate lymphoid cells (ILC) are lymphocytes lacking rearranged antigen receptors such as those expressed by T and B cells. ILC are important effector and regulatory cells of the innate immune system, controlling lymphoid organogenesis, tissue inflammation, and homeostasis. The family of ILC consists of cytotoxic NK cells and the more recently described noncytotoxic group 1, 2, and 3 ILC. The classification of noncytotoxic ILC—in many aspects—mirrors that of T helper cells, which is based on the expression of master transcription factors and signature cytokines specific for each subset. The IL‐22 producing RORγt+ ILC3 subset was recently found to be critical in the prevention of intestinal graft‐versus‐host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) via strengthening the intestinal mucosal barrier. In this review, we summarize the current view of the immunological functions of human noncytotoxic ILC subsets and discuss the potentially beneficial features of IL‐22 producing ILC3 in improving allo‐HCT efficacy by attenuating susceptibility to GVHD. In addition, we explore the possibility of other ILC subsets playing a role in GVHD.

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“…3,4 NKp46 is expressed by NK cells and group 1 and 3 innate lymphoid cells (ILCs). 5-7 NKp46 is encoded by Ncr1 and associates with the ITAM-containing CD3ζ or FcRγ polypeptides. Several endogenous ligands of NKp46 have been described including the complement factor P, 8 the intracellular filamentous cytoskeletal protein vimentin expressed on the surface of Mycobacterium tuberculosis –infected monocytes, 9 and several viral proteins such as hemagglutinin and hemagglutinin neuraminidases of the influenza, 10,11 Sendai, 12 Newcastle disease, 13 ectromelia and vaccinia viruses.…”

Section: Introductionmentioning

confidence: 99%

A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets

et al. 2018

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NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCRB6C14R strain. Ly5.1C14R NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors in vivo. Expression of the mutant NKp46C14R in 293T cells showed that NKp46 protein trafficking to the cell surface was compromised. Although Ly5.1C14R mice had normal number of NK cells, they showed an increased number of early maturation stage NK cells. CD49a+ILC1s were also increased but these cells lacked the expression of TRAIL. ILC3s that expressed NKp46 were not detectable and were not apparent when examined by T-bet expression. Thus, the C14R mutation reveals that NKp46 is important for NK cell and ILC differentiation, maturation and function.SignificanceInnate lymphoid cells (ILCs) play important roles in immune protection. Various subsets of ILCs express the activating receptor NKp46 which is capable of recognizing pathogen derived and tumor ligands and is necessary for immune protection. Here, we describe a spontaneous point mutation in the signal peptide of the NKp46 protein in congenic Ly5.1 mice which are widely used for tracking cells in vivo. This Ncr1 C14R mutation impairs NKp46 surface expression resulting in destabilization of Ncr1 and accumulation of NKp46 in the endoplasmic reticulum. Loss of stable NKp46 expression impaired the maturation of NKp46+ ILCs and altered the expression of TRAIL and T-bet in ILC1 and ILC3, respectively.

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Microbial Flora Drives Interleukin 22 Production in Intestinal NKp46+ Cells that Provide Innate Mucosal Immune Defense

Cited by 994 publications

References 55 publications

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

Innate Lymphoid Cells in Graft-Versus-Host Disease

A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets

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