ILC3 function as a double-edged sword in inflammatory bowel diseases

Published on Apr 8, 2019in Cell Death and Disease6.304
· DOI :10.1038/S41419-019-1540-2
Boning Zeng3
Estimated H-index: 3
(JNU: Jinan University),
Shengnan Shi2
Estimated H-index: 2
(JNU: Jinan University)
+ 3 AuthorsFeiyue Xing12
Estimated H-index: 12
(JNU: Jinan University)
Inflammatory bowel diseases (IBD), composed mainly of Crohn’s disease (CD) and ulcerative colitis (UC), are strongly implicated in the development of intestinal inflammation lesions. Its exact etiology and pathogenesis are still undetermined. Recently accumulating evidence supports that group 3 innate lymphoid cells (ILC3) are responsible for gastrointestinal mucosal homeostasis through moderate generation of IL-22, IL-17, and GM-CSF in the physiological state. ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR− ILC3 or NCR+ ILC3 function and the bias of NCR+ ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state. Herein, we feature the group 3 innate lymphoid cells’ development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy.
📖 Papers frequently viewed together
38 Citations
7 Authors (Sofia Buonocore, ..., Fiona Powrie)
845 Citations
709 Citations
#2Herbert TilgH-Index: 96
Last. Tim Raine (Cambridge University Hospitals NHS Foundation Trust)H-Index: 27
view all 3 authors...
IL-12 and IL-23 are closely related cytokines with important roles in the regulation of tissue inflammation. Converging evidence from studies in mice, human observational studies and population genetics supports the importance of these cytokines in the regulation of mucosal inflammation in the gut in particular. Ustekinumab, a therapeutic antibody targeting both cytokines is now widely licensed for the treatment of Crohn’s disease, including in Europe, the USA, Canada and Japan, whilst agents ta...
137 CitationsSource
#1Mathias L. Richard ('ENS Paris': École Normale Supérieure)H-Index: 19
#2Harry Sokol ('ENS Paris': École Normale Supérieure)H-Index: 68
The gut microbiota is a dense and diverse ecosystem that is involved in many physiological functions as well as in disease pathogenesis. It is dominated by bacteria, which have been extensively studied in the past 15 years; however, other microorganisms, such as fungi, phages, archaea and protists, are also present in the gut microbiota. Exploration of the fungal component, namely, the mycobiota, is at an early stage, and several specific technical challenges are associated with mycobiota analys...
113 CitationsSource
#1Imke AtreyaH-Index: 20
#2Markus KindermannH-Index: 8
Last. Stefan WirtzH-Index: 63
view all 3 authors...
Abstract Colorectal cancer (CRC) is a highly prominent cause of cancer-related deaths worldwide. Although the functions of immune cells in the colorectal tumor microenvironment are complex and heterogeneous, dysregulated changes in the composition and activation state of immune cells are believed to represent key events supporting the establishment of pro- or anti-tumorigenic immune states. Recently, innate lymphoid cells (ILCs) emerged as central innate immune mediators during both gastrointest...
15 CitationsSource
#1Jonathan P SegalH-Index: 11
#2Benjamin H. Mullish (Imperial College London)H-Index: 18
Last. Julian R. Marchesi (Imperial College London)H-Index: 69
view all 8 authors...
The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD. With the utilization of novel systems biology technologies, we can no...
27 CitationsSource
#1Yu Anne Yap (Monash University, Clayton campus)H-Index: 6
#2Eliana Mariño (Monash University, Clayton campus)H-Index: 20
​The rising global incidence of autoimmune and inflammatory conditions can be attributed to changes in the large portion of the immune system that belongs to our gastrointestinal tract (GI). The intestinal immune system serves as gatekeepers to prevent pathogenic invasions through the gut mucosa and maintain homeostasis. Inappropriate immune responses against food and microbial antigens can cause inflammatory disorders such as inflammatory bowel disease (IBD) and celiac disease. Diet influences ...
30 CitationsSource
#1Hamed Khalili (Harvard University)H-Index: 34
#2Simon S.M. Chan (UEA: University of East Anglia)H-Index: 16
Last. Andrew T. ChanH-Index: 110
view all 6 authors...
Crohn’s disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the comple...
79 CitationsSource
#1Sascha CordingH-Index: 13
#2Jasna Medvedovic (French Institute of Health and Medical Research)H-Index: 3
Last. Gérard Eberl (French Institute of Health and Medical Research)H-Index: 71
view all 6 authors...
: Natural killer (NK) cells and lymphoid tissue inducer (LTi) cells were discovered more than 40 and 20 years ago, respectively. These two cell types were initially studied for their unique functions in the elimination of infected or transformed cells, and in the development of lymphoid tissues. It took an additional 10 years to realize that NK cells and LTi cells were members of a larger family of innate lymphoid cells (ILCs), whose phenotypes and functions mirror those of T cells. Many mouse m...
13 CitationsSource
#1Boning Zeng (JNU: Jinan University)H-Index: 3
#2Shengnan Shi (JNU: Jinan University)H-Index: 2
Last. Feiyue Xing (JNU: Jinan University)H-Index: 12
view all 4 authors...
7 CitationsSource
#1Arie Levine (TAU: Tel Aviv University)H-Index: 27
#2Rotem Sigall Boneh (TAU: Tel Aviv University)H-Index: 8
Last. Eytan Wine (U of A: University of Alberta)H-Index: 29
view all 3 authors...
Recent advances in basic and clinical science over the last 3 years have dramatically altered our appreciation of the role of diet in inflammatory bowel diseases (IBD). The marked increase in incidence of these diseases along with the important role of non-genetic susceptibility among patients with IBD has highlighted that these diseases have a strong environmental component. Progress in the field of microbiome and IBD has demonstrated that microbiome appears to play an important role in pathoge...
104 CitationsSource
#1Atsushi Mizoguchi (Kurume University)H-Index: 11
#2Arisa Yano (Kurume University)H-Index: 1
Last. Emiko Mizoguchi (Kurume University)H-Index: 70
view all 6 authors...
IL-22 is a relatively new cytokine that is characterized by several unique biological properties. In the intestines, the effect of IL-22 is restricted mainly to non-lymphoid cells such as epithelial cells. Interestingly, the expression pattern and major cellular source of IL-22 have distinct difference between large and small intestines. IL-22 possesses an ability to constitutively activate STAT3 for promoting epithelial cell regeneration and reinforcing mucosal barrier integrity through stimula...
66 CitationsSource
Cited By60
#1Min Yang (Tianjin Medical University General Hospital)
#2Yu Gu (Tianjin Medical University General Hospital)
Last. Hailong Cao (Tianjin Medical University General Hospital)
view all 10 authors...
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metabolism) and ...
#1Lin Yang (UM: University of Macau)H-Index: 1
#2Hua Luo (UM: University of Macau)H-Index: 4
Last. Yitao Wang (UM: University of Macau)H-Index: 80
view all 8 authors...
Abstract null null Background null Inflammatory bowel disease (IBD) is a chronic idiopathic disease that is characterized by inflammation of the gastrointestinal tract. Proper management of IBD requires both early diagnosis and novel therapies and management programs. Many reports have suggested that Chinese medicine has unique properties favorable to the treatment of IBD. However, there are no systematic analyses on this topic. null null null Purpose null This review summarizes recent studies t...
Despite considerable epidemiological evidence indicating comorbidity between metabolic disorders, such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, and inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, as well as common pathophysiological features shared by these two categories of diseases, the relationship between their pathogenesis at molecular levels are not well described. Intestinal barrier dysfunction is a characteristic pathological ...
#1Zhen Duan (CSU: Central South University)H-Index: 2
#2Mandie Liu (CSU: Central South University)
Last. Yizhou Zou (CSU: Central South University)H-Index: 2
view all 15 authors...
As the direct contacting site for pathogens and allergens, the mucosal barrier plays a vital role in the lungs and intestines. Innate lymphoid cells (ILCs) are particularly resident in the mucosal barrier and participate in several pathophysiological processes, such as maintaining or disrupting barrier integrity, preventing various pathogenic invasions. In the pulmonary mucosae, ILCs sometimes aggravate inflammation and mucus hypersecretion but restore airway epithelial integrity and maintain lu...
During the COVID-19 pandemic, many studies have been carried out to evaluate different immune system components to search for prognostic biomarkers of the disease. A broad multiparametric antibody panel of cellular and humoral components of the innate and the adaptative immune response in patients with active SARS-CoV-2 infection has been evaluated in this study. A total of 155 patients were studied at admission into our center and were categorized according to the requirement of oxygen therapy ...
#1Oluwabunmi O. Olaloye (Yale University)
#2Peng Liu (University of Pittsburgh)H-Index: 6
view all 20 authors...
Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the...
#1Givanna H. Putri (USYD: University of Sydney)H-Index: 2
Mapping the dynamics of immune cell populations over time or disease-course is key to understanding immunopathogenesis and devising putative interventions. We present TrackSOM, an algorithm which delineates cellular populations and tracks their development over a time- or disease-course of cytometry datasets. We demonstrate TrackSOM-enabled elucidation of the immune response to West Nile Virus infection in mice, uncovering heterogeneous sub-populations of immune cells and relating their function...
#1Ji-Hyun Kim (New Generation University College)H-Index: 3
Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. ILCs can be categorized into three groups on the basis of the transcription factors that direct their functions and the cytokines they produce. Notably, these functions parallel the effector functions of T lymphocytes. ILCs play a frontline role in host defense and tissue homeostasis by responding rapidly to environmental factors, conducting effector responses in a tissue-specific manner, and interacting...
2 CitationsSource
#1Haitham Hajjo (Technion – Israel Institute of Technology)H-Index: 3
#2Naama Geva-Zatorsky (CIFAR: Canadian Institute for Advanced Research)H-Index: 19
The gut microbiota and the immune system have co-evolved to interact and cooperate in many ways. A recent study characterizing the immunomodulatory effects of over 60 different human-derived gut microbes across phyla showed that bacteria-induced immunomodulations are not dictated by the bacterial phylogeny. Yet, it remains unclear whether strains from the same species induce the same immunomodulatory effects on the host. We analyzed the strain-level data from this recent study and found that str...
#1Metin Yusuf Gelmez (Istanbul University)H-Index: 3
#2Suzan Çinar (Istanbul University)H-Index: 8
Last. Günnur Deniz (Istanbul University)H-Index: 24
view all 9 authors...
ABSTRACT Innate lymphoid cells (ILCs) are lymphoid cells that have important effector and regulatory functions in innate immunity and tissue remodeling. Uncontrolled activation and proliferation of ILCs can contribute to inflammatory autoimmune diseases. Behcet's disease (BD) is a complex systemic inflammatory disorder of unknown etiology. It has been shown that natural killer (NK) cells may play an immunoregulatory role in BD, however the role of ILCs is unknown. In this study, the levels and f...
1 CitationsSource