Innate lymphoid cells--a proposal for uniform nomenclature.
University of Amsterdam1, University of Pennsylvania2, Washington University in St. Louis3, University of Freiburg4, Pasteur Institute5, University of California, San Francisco6, Laboratory of Molecular Biology7, VU University Amsterdam8, John Radcliffe Hospital9, Centre national de la recherche scientifique10, French Institute of Health and Medical Research11
TL;DR: It is proposed that ILCs should be categorized into three groups based on the cytokines that they can produce and the transcription factors that regulate their development and function.
Abstract: Innate lymphoid cells (ILCs) are a family of developmentally related cells that are involved in immunity and in tissue development and remodelling. Recent research has identified several distinct members of this family. Confusingly, many different names have been used to characterize these newly identified ILC subsets. Here, we propose that ILCs should be categorized into three groups based on the cytokines that they can produce and the transcription factors that regulate their development and function.
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TL;DR: This Review provides a comprehensive overview of how IECs maintain host–commensal microbial relationships and immune cell homeostasis in the intestine.
Abstract: The abundance of innate and adaptive immune cells that reside together with trillions of beneficial commensal microorganisms in the mammalian gastrointestinal tract requires barrier and regulatory mechanisms that conserve host-microbial interactions and tissue homeostasis. This homeostasis depends on the diverse functions of intestinal epithelial cells (IECs), which include the physical segregation of commensal bacteria and the integration of microbial signals. Hence, IECs are crucial mediators of intestinal homeostasis that enable the establishment of an immunological environment permissive to colonization by commensal bacteria. In this Review, we provide a comprehensive overview of how IECs maintain host-commensal microbial relationships and immune cell homeostasis in the intestine.
2,046 citations
TL;DR: The key properties of IL-1 family members are reviewed, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.
1,545 citations
Cites background from "Innate lymphoid cells--a proposal f..."
...The discovery of innate lymphoid cells and the dissection of pathways of T cell differentiation have revealed essential functions for IL-1, IL-18, and IL-33 and have opened vistas on their functions (O’Shea and Paul, 2010; Spits et al., 2013)....
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...The perception that IL-1 affects lymphoid cells has waned for a long time to be revisited with the realization that polarized T cell and ILC differentiation and function involves members of the IL-1 family (Figure 5) (O’Shea and Paul, 2010; Spits et al., 2013)....
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...ation have revealed essential functions for IL-1, IL-18, and IL-33 and have opened vistas on their functions (O’Shea and Paul, 2010; Spits et al., 2013)....
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...ILCs are a complex and heterogeneous group of lymphoid cells involved in innate immunity and tissue remodeling (Spits et al., 2013)....
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TL;DR: A metabolic pathway whereby Trp metabolites from the microbiota balance mucosal reactivity in mice is described, whereby highly adaptive lactobacilli are expanded and produce an aryl hydrocarbon receptor (AhR) ligand-indole-3-aldehyde-that contributes to AhR-dependent Il22 transcription.
1,540 citations
Cites background from "Innate lymphoid cells--a proposal f..."
...referred to as group 3 ILCs (ILC3s) (Spits et al., 2013)....
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...In the gastrointestinal tract, dietderived AhR ligands promote local IL-22 production (Lee et al., 2012) by innate lymphoid cells (ILCs) (Qiu et al., 2012), now 372 Immunity 39, 372–385, August 22, 2013 ª2013 Elsevier Inc. referred to as group 3 ILCs (ILC3s) (Spits et al., 2013)....
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TL;DR: This work summarizes the studies that formally identified innate lymphoid cells and highlights their emerging roles in controlling tissue homeostasis in the context of infection, chronic inflammation, metabolic disease and cancer.
Abstract: The innate immune system is composed of a diverse array of evolutionarily ancient haematopoietic cell types, including dendritic cells, monocytes, macrophages and granulocytes. These cell populations collaborate with each other, with the adaptive immune system and with non-haematopoietic cells to promote immunity, inflammation and tissue repair. Innate lymphoid cells are the most recently identified constituents of the innate immune system and have been the focus of intense investigation over the past five years. We summarize the studies that formally identified innate lymphoid cells and highlight their emerging roles in controlling tissue homeostasis in the context of infection, chronic inflammation, metabolic disease and cancer.
1,281 citations
Aix-Marseille University1, Cornell University2, Washington University in St. Louis3, Charité4, French Institute of Health and Medical Research5, Pasteur Institute6, Keio University7, University of California, San Francisco8, Laboratory of Molecular Biology9, VU University Amsterdam10, University of Oxford11, University of Amsterdam12
TL;DR: The advances in ILC biology over the past decade are distill the advances to refine the nomenclature of ILCs and highlight the importance of I LCs in tissue homeostasis, morphogenesis, metabolism, repair, and regeneration.
1,252 citations
Cites background or methods from "Innate lymphoid cells--a proposal f..."
...Innate lymphoid cells (ILCs), which lack adaptive antigen receptors generated by the recombination of genetic elements, are the innate counterparts of T lymphocytes (Spits et al., 2013; Eberl et al., 2015; Artis andSpits, 2015)....
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...We first proposed a common nomenclature for ILCs and ILC subsets in 2013 (Spits et al., 2013)....
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TL;DR: The identification and functional characterization of a new innate type-2 immune effector leukocyte that is named the nuocyte is presented, which represents a critically important innate effector cell in type- 2 immunity.
Abstract: Innate immunity provides the first line of defence against invading pathogens and provides important cues for the development of adaptive immunity. Type-2 immunity-responsible for protective immune responses to helminth parasites and the underlying cause of the pathogenesis of allergic asthma-consists of responses dominated by the cardinal type-2 cytokines interleukin (IL)4, IL5 and IL13 (ref. 5). T cells are an important source of these cytokines in adaptive immune responses, but the innate cell sources remain to be comprehensively determined. Here, through the use of novel Il13-eGFP reporter mice, we present the identification and functional characterization of a new innate type-2 immune effector leukocyte that we have named the nuocyte. Nuocytes expand in vivo in response to the type-2-inducing cytokines IL25 and IL33, and represent the predominant early source of IL13 during helminth infection with Nippostrongylus brasiliensis. In the combined absence of IL25 and IL33 signalling, nuocytes fail to expand, resulting in a severe defect in worm expulsion that is rescued by the adoptive transfer of in vitro cultured wild-type, but not IL13-deficient, nuocytes. Thus, nuocytes represent a critically important innate effector cell in type-2 immunity.
1,896 citations
TL;DR: In this article, a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity was reported. But these cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R.
Abstract: Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines. Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue 'FALC' (fat-associated lymphoid cluster). FALC Lin(-)c-Kit(+)Sca-1(+) cells are distinct from lymphoid progenitors and lymphoid tissue inducer cells. These cells proliferate in response to IL2 and produce large amounts of T(H)2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells. Indeed, FALC Lin(-)c-Kit(+)Sca-1(+) cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection. After helminth infection and in response to IL33, FALC Lin(-)c-Kit(+)Sca-1(+) cells produce large amounts of IL13, which leads to goblet cell hyperplasia-a critical step for helminth expulsion. In mice devoid of FALC Lin(-)c-Kit(+)Sca-1(+) cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'.
1,649 citations
TL;DR: A critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus is demonstrated.
Abstract: Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor a-chain (CD25), IL-7 receptor a-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus.
1,270 citations
TL;DR: The characterization of a human NK cell subset located in mucosa-associated lymphoid tissues, such as tonsils and Peyer’s patches, which is hard-wired to secrete interleukin (IL)-22, IL-26 and leukaemia inhibitory factor is reported.
Abstract: A previously unrecognized subset of human natural killer (NK) lymphocytes is reported. These 'NK-22' cells are selectively localized in tonsil and gut mucosa and, in contrast to conventional NK cells, are poorly cytotoxic and secrete little or no interferon. Rather, they specialize in the secretion of interleukin 22 (IL-22), IL-26 and leukaemia inhibitory factor, all of which have been implicated in the protection of epithelia. The properties of NK-22 cells are consistent with an anti-inflammatory response that may contribute to the maintenance of mucosal integrity. This study identifies a subset of natural killer (NK) cells in the gut that produce interleukin-22, rather than mediate target cell killing. It is suggested that these NK cells, referred to as NK-22 cells, may help constrain inflammation and contribute to the maintenance of mucosal integrity. Natural killer (NK) cells are classically viewed as lymphocytes that provide innate surveillance against virally infected cells and tumour cells through the release of cytolytic mediators and interferon (IFN)-γ. In humans, blood CD56dim NK cells specialize in the lysis of cell targets1. In the lymph nodes, CD56bright NK cells secrete IFN-γ cooperating with dendritic cells and T cells in the generation of adaptive responses1,2. Here we report the characterization of a human NK cell subset located in mucosa-associated lymphoid tissues, such as tonsils and Peyer’s patches, which is hard-wired to secrete interleukin (IL)-22, IL-26 and leukaemia inhibitory factor. These NK cells, which we refer to as NK-22 cells, are triggered by acute exposure to IL-23. In vitro, NK-22-secreted cytokines stimulate epithelial cells to secrete IL-10, proliferate and express a variety of mitogenic and anti-apoptotic molecules. NK-22 cells are also found in mouse mucosa-associated lymphoid tissues and appear in the small intestine lamina propria during bacterial infection, suggesting that NK-22 cells provide an innate source of IL-22 that may help constrain inflammation and protect mucosal sites.
1,197 citations
TL;DR: The results suggest that IL-25, derived from Th2 T cells, is capable of amplifying allergic type inflammatory responses by its actions on other cell types.
1,154 citations