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innate lymphoid cells in tissue homeostasis and diseases

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World Journal of Hepatology 2017年第23期9卷 979-989页

作者： Aline Ignacio Cristiane Naffah Souza Breda Niels Olsen Saraiva Camara Laboratory of Transplantation Immunobiology Institute of Biomedical SciencesDepartment of ImmunologyUniversity of Sao PauloSP 05508-900Brazil

innate lymphoid cells(ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets(ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

关键词： innate lymphoid cells Intestine Liver Homeostasis Inflammatory diseases

NKR-P1B expression in gut-associated innate lymphoid cells is required for the control of gastrointestinal tract infections

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Cellular & Molecular Immunology 2019年第11期16卷 868-877页

作者： Elias Abou-Samra Zachary Hickey Oscar A.Aguilar Michal Scur Ahmad Bakur Mahmoud Sergey Pyatibrat Megan M.Tu Jeffrey Francispillai Arthur Mortha James R.Carlyle Mir Munir A.Rahim Andrew P.Makrigiannis Department of Biochemistry Microbiology and ImmunologyUniversity of Ottawa451 Smyth RoadOttawaON K1H 8M5Canada Department of Immunology University of Toronto1 King’s College CircleTorontoON M5S 1A8Canada Sunnybrook Research Institute 2075 Bayview AvenueTorontoON M4N 3M5Canada Department of Microbiology and Immunology Dalhousie University5850 College StreetHalifaxNS B3H 4R2Canada College of Applied Medical Sciences Taibah UniversityMadinah MunawwarahSaudi Arabia Division of Anatomical Pathology Department of Pathology and Laboratory MedicineThe Ottawa HospitalUniversity of Ottawa501 Smyth RoadOttawaON K1H 8L6Canada

Helper-type innate lymphoid cells(ILC)play an important role in intestinal *** of the NKR-P1 gene family are expressed in various innate immune cells,including natural killer(NK)cells,and their cognate Clr ligand family members are expressed in various specialized tissues,including the intestinal epithelium,where they may play an important role in mucosalassociated innate immune *** this study,we show that the inhibitory NKR-P1B receptor,but not the Ly49 receptor,is expressed in gut-resident NK cells,ILC,and a subset ofγδT cells in a tissue-specific ***3 cells constitute the predominant cell subset expressing NKR-P1B in the gut lamina *** known NKR-P1B ligand Clr-b is broadly expressed in gut-associated cells of hematopoietic *** genetic deletion of NKR-P1B results in a higher frequency and number of ILC3 andγδT cells in the gut lamina ***,the function of gut-resident ILC3,NK,andγδT cells in NKR-P1B-deficient mice is impaired during gastrointestinal tract infection by Citrobacter rodentium or Salmonella typhimurium,resulting in increased systemic bacterial dissemination in NKR-P1B-deficient *** findings highlight the role of the NKR-P1B:Clr-b recognition system in the modulation of intestinal innate immune cell functions.

关键词： innate lymphoid cells Natural killer cells Gut-associated immune cells NKR-P1B receptor innate immunity

The protective roles of integrin α4β7 and Amphiregulin-expressing innate lymphoid cells in lupus nephritis

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Cellular & Molecular Immunology 2024年第7期21卷 723-737页

作者： Seungwon Ryu Kyung Ah Kim Jinwoo Kim Dong Hun Lee Yong-Soo Bae Hajeong Lee Byoung Choul Kim Hye Young Kim Department of Microbiology Gachon University College of MedicineIncheon21999South Korea Department of Nano-Bioengineering Incheon National UniversityIncheon22012South Korea Laboratory of Mucosal Immunology Department of Biomedical SciencesSeoul National University College of MedicineSeoul03080South Korea Department of Dermatology Seoul National University College of MedicineSeoul03080South Korea Laboratory of Cutaneous Aging Research Biomedical Research InstituteSeoul National University HospitalSeoul03080South Korea Institute of Human–Environment Interface Biology Medical Research CenterSeoul National UniversitySeoul03080South Korea Department of Biological Sciences SRC Center for Immune Research on Non-lymphoid OrgansSungkyunkwan UniversitySuwon16419South Korea Department of Biological Sciences Sungkyunkwan UniversitySuwon16419South Korea Division of Nephrology Department of Internal MedicineSeoul National University Hospital and Seoul National University College of MedicineSeoul03080South Korea Institute of Allergy and Clinical Immunology Seoul National University Medical Research CenterSeoul National University College of MedicineSeoul03080South Korea

Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of integrin α4β7 in mediating renal ILC2 adhesion and function. We found that integrin α4β7 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, integrin α4β7 knockdown reduced the production of the reparative cytokine amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7/9 signaling within the kidney microenvironment downregulates integrin α4β7 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated integrin α4β7 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.

关键词： innate lymphoid cells Tissue residency Adhesion molecules Integrins Kidney Lupus nephritis Amphiregulin

Sensing of physiological regulators by innate lymphoid cells

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Cellular & Molecular Immunology 2019年第5期16卷 442-451页

作者： Cyril Seillet Nicolas Jacquelot Molecular Immunology Division Walter and Eliza Hall Institute of Medical ResearchMelbourneVIC 3052Australia Department of Medical Biology University of MelbourneMelbourneVIC 3010Australia

Maintenance of homeostasis and immune protection rely on the coordinated action of different physiological *** communication between the immune system and physiological systems is required to sense and restore any disruption of *** transcriptomic analyses of innate lymphoid cells(ILCs)from different tissues have revealed that ILCs express a large array of receptors involved in the recognition of neuropeptides,hormones and metabolic *** rapidly secrete effector cytokines that are central in the development and activation of early immune responses,but they also constitutively secrete mediators that are important for tissue *** achieve these functions effectively,ILCs integrate intrinsic and extrinsic signals that modulate their constitutive and induced *** of the regulation of ILCs by physiological regulators leads to altered immune responses with harmful consequences for the *** understanding of these complex interactions between the immune system and physiological mediators is crucial to decipher the events leading to the protective versus pathological effects of these cells.

关键词： innate lymphoid cells immunity immune protection homeostasis

The transcription factor RelB restrains group 2 innate lymphoid cells and type 2 immune pathology in vivo

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Cellular & Molecular Immunology 2021年第1期18卷 230-242页

作者： Lei Zhang Yuanlin Ying Shuqiu Chen Preston R.Arnold Fafa Tian Laurie J.Minze Xiang Xiao Xian C.Li Immunobiology and Transplant Science Center and Department of SurgeryHouston Methodist HospitalTexas Medical CenterHoustonTexasUSA Department of Neurology Xiangya HospitalCentral South UniversityChangshaChina Department of Urology Southeast University Zhongda HospitalNanjingChina Department of Surgery Weill Cornell Medical College of Cornell UniversityNew YorkNYUSA

The exact relationships between group 2 innate lymphoid cells(ILC2s)and Th2 cells in type 2 pathology,as well as the mechanisms that restrain the responses of these cells,remain poorly *** we examined the roles of ILC2s and Th2 cells in type 2 lung pathology in vivo using germline and conditional fie/b-deficient *** found that mice with germline deletion of Relb^(-/-)spontaneously developed prominent type 2 pathology in the lung,which contrasted sharply with mice with T-cell-specific Relb deletion(Relb^(f/f)Cd4-Cre),which were healthy with no observed autoimmune *** also found that in contrast to wild-type B6 mice,Rel6-defident mice showed markedly expanded ILC2s but not ILC1s or ***,adoptive transfer of naive CD4^(+)T cells into Rag1^(-/-)Relb^(-/-)hosts induced prominent type 2 lung pathology,which was inhibited by depletion of ***,we showed that Relb deletion led to enhanced expression of Bcl11b,a key transcription factor for *** concluded that RelB plays a critical role in restraining ILC2s,primarily by suppressing Bcl11b activity,and consequently inhibits type 2 lung pathology in vivo.

关键词： Allergic inflammation innate lymphoid cells NF-kB RelB Th2 cells type 2 pathology

Guards at the gate： physiological and pathological roles of tissue-resident innate lymphoid cells in the lung

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Protein & Cell 2017年第12期8卷 878-895页

作者： Hang Cheng Chengyan Jin Jing Wu Shan Zhu Yong-Jun Liu Jingtao Chen Institute of Translational Medicine The First Hospital Jilin University Changchun 130061 China Department of Pediatrics The First Hospital JUin University Changchun 130021 China Department of Thoracic Surgery The Second Hospital Jilin University Changchun 130041 China Sanofi Research and Development Cambridge MA 02139 USA

The lung Is an Important open organ and the primary site of respiration. Many *** diseases develop in the lung, e.g., pneumonia, asthma, chronic obstructive pulmonary diseases （COPDs）, pulmonary fibrosis, and lung cancer. In the lung, innate Immunity serves as the frontline in both anti-irritant response and anti-tumor defense and is also critical for mucosal homeostasis; thus, it plays an important role In containing these pul- monary diseases. innate lymphoid cells （ILCs）, charac. terized by their strict tissue residence and distinct function in the mucosa, are attracting Increased atten. tion In innate Immunity. Upon sensing the danger slg- nals from damaged epithelium, ILCs activate, proliferate, and release numerous cytoklnes with specific local functions; they also participate in mucosal immune- surveillance, Immune-regulation, and homeostasis. However, when their functions become uncontrolled, ILCs can enhance pathological states and Induce dis- eases. In this review, we discuss the physiologicel and pathological functions of ILC subsets 1 to 3 in the lung, and how the pathogenic environment affects the func- tion and plasticity of ILCs.

关键词： lung innate lymphoid cells pulmonarydiseases regional immunity

innate lymphoid cells in Normal Pregnancy and Pregnancy-Related Diseases

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Reproductive and Developmental Medicine 2020年第1期4卷 53-59页

作者： Cheng-Jie Wang Yi Yu Ming-Qing Li Wei-Rong Gu Laboratory for Reproductive Immunology Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesObstetrics and Gynecology Hospital of Fudan UniversityShanghai 200011China Department of Obstetrics Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200011China Laboratory for Reproductive Immunology Institute of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan UniversityShanghai 200082China Laboratory for Reproductive Immunology NHC Key Laboratory of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research)Fudan UniversityShanghai 230032China

innate lymphoid cells(ILCs)are a group of lymphocytes without diversified antigen receptors encoded by gene rearrangement on T and B ***,which are tissue-resident innate immune cells,expressed particularly in the mucosa or the barrier surface,contribute to the formation of lymphoid organs,the maintenance of tissue homeostasis,and the regulation of antimicrobial *** has been recently reported that ILCs were enriched at the maternal-fetal *** a successful pregnancy,the maternal immune system must tolerate a fetus as an *** the new defined of ILCs,a number of studies have shown that three types of ILCs are involved in embryonic development and pregnancy maintenance as well as the occurrence and development of pregnancy-related *** article reviews the types and roles of ILCs in normal pregnancy and pregnancy-related diseases.

关键词： Immune innate lymphoid cells Maternal-Fetal Interface Pregnancy

The origin and role of innate lymphoid cells in the lung

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Journal of Medical Colleges of PLA(China) 2016年第4期31卷 219-229页

作者： Deng-Ming Lai Qiang Shu Jie Fan Department of Cardiovascular Surgery the Children’s Hospital of Zhejiang University School of Medicine Department of Surgery University of Pittsburgh School of Medicine Research and Development Veterans Affairs Pittsburgh Healthcare System

innate lymphoid cells(ILCs),a newly identified member of the lymphoid population,play a critical role in the transition from innate to adaptive immunity in host *** are important in mucosal barrier immunity,tissue homeostasis,and immune regulation throughout the *** alterations in ILC responses in lung diseases have been observed and *** evidence has shown that ILCs are importantly involved in the pathogenesis and development of a variety of lung diseases,i.e.,helminth infections,allergic airway inflammation,and airway ***,as a tissue-resident cell population,the role of ILCs in the lung remains poorly *** this review,we discuss the role of ILCs in lung diseases,the mechanisms underlying the ILCmediated regulation of immunity,and the therapeutic potential of modulating ILC responses.

关键词： innate lymphoid cells innate immunity Lung diseases Airway Cell interaction Cytokines

innate lymphoid cells:A Promising New Regulator in Fibrotic Diseases

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Innate Lymphoid Cells:A Promising New Regulator in Fibrotic ...