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Innate lymphoid cells liver

Xing He, Jun Xie, Yange Wang, Xiaobin Fan, Qin Su, Yue Sun, Nanhang Lei, Dongmei Zhang, Guangping Gao, Weiqing Pan
The type 2 immune response is the central mechanism of disease progression in schistosomiasis, but the signals that induce it after infection remain elusive. Aberrant microRNA (miRNA) expression is a hallmark of human diseases including schistosomiasis, and targeting the deregulated miRNA can mitigate disease outcomes. Here, we demonstrate that efficient and sustained elevation of miR-203-3p in liver tissues, using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), protects mice against lethal schistosome infection by alleviating hepatic fibrosis...
March 19, 2018: PLoS Pathogens
Rachel P Frawley, Matthew Smith, Mark F Cesta, Schantel Hayes-Bouknight, Chad Blystone, Grace E Kissling, Shawn Harris, Dori Germolec
Poly- and perfluoroalkyl substances (PFAS) are chemically and thermally stable, hydrophobic, lipophobic compounds used in stain repellants and water and oil surfactants, and associated with immunosuppression and peroxisome proliferator activity. Perfluoro-n-decanoic acid (PFDA, (CF3 (CF2 )8 COOH), a fluorinated straight chain fatty acid compound, is reported to induce thymic atrophy and reversible bone marrow hypocellularity in rodent models. The objective of this study was to assess potential immunotoxicity of PFDA, due to its structural similarity to other immunosuppressive PFASs...
December 2018: Journal of Immunotoxicology
Susanna S Ng, Fernando Souza-Fonseca-Guimaraes, Fabian de Labastida Rivera, Fiona H Amante, Rajiv Kumar, Yulong Gao, Meru Sheel, Lynette Beattie, Marcela Montes de Oca, Camille Guillerey, Chelsea L Edwards, Rebecca J Faleiro, Teija Frame, Patrick T Bunn, Eric Vivier, Dale I Godfrey, Daniel G Pellicci, J Alejandro Lopez, Katherine T Andrews, Nicholas D Huntington, Mark J Smyth, James McCarthy, Christian R Engwerda
Objectives: Innate lymphoid cells (ILCs) share many characteristics with CD4+ T cells, and group 1 ILCs share a requirement for T-bet and the ability to produce IFNγ with T helper 1 (Th1) cells. Given this similarity, and the importance of Th1 cells for protection against intracellular protozoan parasites, we aimed to characterise the role of group 1 ILCs during Plasmodium infection. Methods: We quantified group 1 ILCs in peripheral blood collected from subjects infected with with Plasmodium falciparum 3D7 as part of a controlled human malaria infection study, and in the liver and spleens of Pc AS-infected mice...
2018: Clinical & Translational Immunology
Yuejin Liang, Panpan Yi, Denley Ming Kee Yuan, Zuliang Jie, Zakari Kwota, Lynn Soong, Yingzi Cong, Jiaren Sun
Viral hepatitis is still a public health problem affecting several million people around the world. Neutrophils are polymorphonuclear cells that have a critical role in antibacterial infection. However, the role of neutrophils in viral infection is not fully understood. By using a mouse model of lymphocytic choriomeningitis virus infection-induced viral hepatitis, we observed increased neutrophil recruitment in the liver accompanied by enhanced CD8+ T-cell responses. Liver neutrophils expressed high levels of immunomodulatory cytokines, such as C-X-C chemokine ligand 2, arginase-1, inducible nitric oxide synthase and interleukin (IL)-10, demonstrating immunosuppressive properties...
February 5, 2018: Cellular & Molecular Immunology
Arundhoti Das, Christelle Harly, Qi Yang, Avinash Bhandoola
Innate lymphoid cells (ILCs) are immune cells that lack specific antigen receptors but possess similar effector functions as T cells. Concordantly, ILCs express many transcription factors known to be important for T cell effector function. ILCs develop from lymphoid progenitors in fetal liver and adult bone marrow. However, the identification of ILC progenitor (ILCP) and other precursors in peripheral tissues raises the question of whether ILC development might occur at extramedullary sites. We discuss central and local generation in maintaining ILC abundance at peripheral sites...
January 12, 2018: Cytokine & Growth Factor Reviews
Hannah C Jeffery, Patrick McDowell, Philipp Lutz, Rebecca E Wawman, Sheree Roberts, Chris Bagnall, Jane Birtwistle, David H Adams, Ye Htun Oo
INTRODUCTION: Innate lymphoid cells (ILC) have been implicated in the initiation of inflammation and fibrosis in mice. However, ILC have not been characterized in inflamed human liver tissue. METHODS: Human intrahepatic lymphocytes were isolated by mechanical digestion and phenotyped by flow cytometry. Conditioned medium from cultures of primary human biliary epithelial cells, stellate cells, fibroblasts and inflamed human liver tissue was used to model the effects of the inflammatory liver environment of ILC phenotype and function...
2017: PloS One
Guillemette Masse-Ranson, Hugo Mouquet, James P Di Santo
PURPOSE OF REVIEW: Immunodeficient mice that lack all lymphocyte subsets and have phagocytic cells that are tolerant of human cells can be stably xenografted with human hematopoietic stem cell as well as other human tissues (fetal liver and thymus) creating 'human immune system' (HIS) mice. HIS mice develop all major human lymphocyte classes (B, T, natural killer, and innate lymphoid cell) and their specialized subsets as well as a variety of myeloid cells (dendritic cell, monocytes, and macrophages) thereby providing a small animal model in which to interrogate human immune responses to infection...
March 2018: Current Opinion in HIV and AIDS
Amy C Prosser, Axel Kallies, Michaela Lucas
Short-term outcomes of solid organ transplantation have improved dramatically over the past several decades; however, long-term survival has remained static over the same time period, and chronic rejection remains a major cause of graft failure. The importance of donor, or 'passenger', lymphocytes to the induction of tolerance to allografts was recognized in the 1990s; however, their precise contribution to graft acceptance or rejection has not been elucidated. Recently, specialized populations of tissue-resident lymphocytes in nonlymphoid organs have been described...
November 14, 2017: Transplantation
Nobuhiro Nakamoto, Takeru Amiya, Ryo Aoki, Nobuhito Taniki, Yuzo Koda, Kentaro Miyamoto, Toshiaki Teratani, Takahiro Suzuki, Sayako Chiba, Po-Sung Chu, Atsushi Hayashi, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Wataru Suda, Yohei Mikami, Nobuhiko Kamada, Hirotoshi Ebinuma, Hidetsugu Saito, Masahira Hattori, Takanori Kanai
Gut-derived microbial antigens trigger the innate immune system during acute liver injury. During recovery, regulatory immunity plays a role in suppressing inflammation; however, the precise mechanism underlying this process remains obscure. Here, we find that recruitment of immune-regulatory classical dendritic cells (cDCs) is crucial for liver tolerance in concanavalin A-induced acute liver injury. Acute liver injury resulted in enrichment of commensal Lactobacillus in the gut. Notably, Lactobacillus activated IL-22 production by gut innate lymphoid cells and raised systemic IL-22 levels...
October 31, 2017: Cell Reports
Shinya Hatano, Tesshin Murakami, Naoto Noguchi, Hisakata Yamada, Yasunobu Yoshikai
We recently found that a unique subset of innate-like γδ T cells develops from the DN2a stage of the fetal thymus independently of the zinc-finger transcription factor B cell leukemia/lymphoma 11b (Bcl11b). Herein, we characterize these Bcl11b-independent γδ T cells in the periphery as CD5(-)NK1.1(+) and Granzyme B(+), and we show that they are capable of producing interferon (IFN)-γ upon T cell receptor stimulation without Ca(2+) influx. In wild-type mice, these cells were sparse in lymphoid tissues but abundant in non-lymphoid tissues, such as the liver...
October 31, 2017: Cell Reports
Martina Molgora, Eduardo Bonavita, Andrea Ponzetta, Federica Riva, Marialuisa Barbagallo, Sébastien Jaillon, Branka Popović, Giovanni Bernardini, Elena Magrini, Francesca Gianni, Santiago Zelenay, Stipan Jonjić, Angela Santoni, Cecilia Garlanda, Alberto Mantovani
Interleukin-1 receptor 8 (IL-1R8, also known as single immunoglobulin IL-1R-related receptor, SIGIRR, or TIR8) is a member of the IL-1 receptor (ILR) family with distinct structural and functional characteristics, acting as a negative regulator of ILR and Toll-like receptor (TLR) downstream signalling pathways and inflammation. Natural killer (NK) cells are innate lymphoid cells which mediate resistance against pathogens and contribute to the activation and orientation of adaptive immune responses. NK cells mediate resistance against haematopoietic neoplasms but are generally considered to play a minor role in solid tumour carcinogenesis...
November 2, 2017: Nature
Orr-El Weizman, Nicholas M Adams, Iona S Schuster, Chirag Krishna, Yuri Pritykin, Colleen Lau, Mariapia A Degli-Esposti, Christina S Leslie, Joseph C Sun, Timothy E O'Sullivan
Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Whether tissue-resident lymphocytes confer early antiviral immunity at local sites of primary infection prior to the initiation of circulating responses is not well understood. Furthermore, the kinetics of initial antiviral responses at sites of infection remain unclear. Here, we show that tissue-resident type 1 innate lymphoid cells (ILC1) serve an essential early role in host immunity through rapid production of interferon (IFN)-γ following viral infection...
November 2, 2017: Cell
Aline Ignacio, Cristiane Naffah Souza Breda, Niels Olsen Saraiva Camara
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)...
August 18, 2017: World Journal of Hepatology
Claire Berthault, Cyrille Ramond, Odile Burlen-Defranoux, Guillaume Soubigou, Sylvestre Chea, Rachel Golub, Pablo Pereira, Paulo Vieira, Ana Cumano
The molecular events that initiate lymphoid-lineage specification remain unidentified because the stages of differentiation during which lineage commitment occurs are difficult to characterize. We isolated fetal liver progenitor cells undergoing restriction of their differentiation potential toward the T cell-innate lymphoid cell lineage or the B cell lineage. Transcripts that defined the molecular signatures of these two subsets were sequentially upregulated in lympho-myeloid precursor cells and in common lymphoid progenitor cells, respectively, and this preceded lineage restriction; this indicates that T cell-versus-B cell commitment is not a binary fate 'decision'...
October 2017: Nature Immunology
Antonia O Cuff, Victoria Male
Mouse liver contains both Eomes-dependent conventional natural killer (cNK) cells and Tbet-dependent liver-resident type I innate lymphoid cells (ILC1). In order to better understand the role of ILC1, we attempted to generate mice that would lack liver ILC1, while retaining cNK, by conditional deletion of Tbet in NKp46+ cells. Here we report that the Ncr1 (iCre)Tbx21 (fl/fl) mouse has a roughly equivalent reduction in both the cNK and ILC1 compartments of the liver, limiting its utility for investigating the relative contributions of these two cell types in disease models...
2017: Wellcome Open Research
Hui Peng, Zhigang Tian
Although natural killer (NK) cells were initially named for their spontaneous tumor-killing capacity, their concept has been greatly expanded with more than 40 years of extensive investigation. Currently, NK cells are known as a heterogeneous population of innate lymphoid cell (ILC) family, consisting of different subsets with unique phenotypic and functional features. Recent studies have shown that tissue-resident NK (trNK) cells, which are distinct from conventional NK (cNK) cells, preferentially distribute in non-lymphoid tissues, such as the liver, uterus, salivary gland, and adipose...
August 9, 2017: Seminars in Immunology
Mariana Resende, Marcos S Cardoso, Ana R Ribeiro, Manuela Flórido, Margarida Borges, António Gil Castro, Nuno L Alves, Andrea M Cooper, Rui Appelberg
IFN-γ is known to be predominantly produced by lymphoid cells such as certain subsets of T cells, NK cells, and other group 1 innate lymphoid cells. In this study, we used IFN-γ reporter mouse models to search for additional cells capable of secreting this cytokine. We identified a novel and rare population of nonconventional IFN-γ-producing cells of hematopoietic origin that were characterized by the expression of Thy1.2 and the lack of lymphoid, myeloid, and NK lineage markers. The expression of IFN-γ by this population was higher in the liver and lower in the spleen...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Meifang Liu, Cai Zhang
Innate lymphoid cells (ILCs) are a recently identified group of innate immune cells lacking antigen-specific receptors that can mediate immune responses and regulate tissue homeostasis and inflammation. ILCs comprise group 1 ILCs, group 2 ILCs, and group 3 ILCs. These ILCs usually localize at mucosal surfaces and combat pathogens by the rapid release of certain cytokines. However, the uncontrolled activation of ILCs can also lead to damaging inflammation, especially in the gut, lung, and skin. Although the physiological and pathogenic roles of ILCs in liver diseases have been attracting increasing attention recently, there has been no systematic review regarding the roles of ILCs in immune-mediated liver diseases...
2017: Frontiers in Immunology
Marianne Forkel, Lena Berglin, Eliisa Kekäläinen, Adrian Carlsson, Emma Svedin, Jakob Michaëlsson, Maho Nagasawa, Jonas S Erjefält, Michiko Mori, Malin Flodström-Tullberg, Annika Bergquist, Hans-Gustaf Ljunggren, Magnus Westgren, Ulrik Lindforss, Danielle Friberg, Carl Jorns, Ewa Ellis, Niklas K Björkström, Jenny Mjösberg
Human innate lymphoid cells have been described to exist in different organs, with functional deregulation of these cells contributing to several disease states. Here, we performed the first detailed characterization of the phenotype, tissue-residency properties, and functionality of ILC1s, ILC2s, and ILC3s in the human adult and fetal liver. In addition, we investigated changes in the ILC compartment in liver fibrosis. A unique composition of tissue-resident ILCs was observed in nonfibrotic livers as compared with that in mucosal tissues, with NKp44- ILC3s accounting for the majority of total intrahepatic ILCs...
August 2017: European Journal of Immunology
Philippe Vasseur, Sarah Dion, Aveline Filliol, Valentine Genet, Catherine Lucas-Clerc, Girard Jean-Philippe, Christine Silvain, Jean-Claude Lecron, Claire Piquet-Pellorce, Michel Samson
Interleukin (IL)-33 has been recently reported to be strongly pro-fibrogenic in various models of liver disease. Our aim was to study the role of endogenous IL-33 in a diet-induced model of steatohepatitis. IL-33 deficient mice and wild type (WT) littermates received a high-fat diet (HFD), or a standard diet for 12 weeks. The HFD-induced steatohepatitis was associated with an upregulation of IL-33 transcripts and protein. An insulin tolerance test revealed lower systemic insulin sensitivity in IL-33-/-HFD mice than in WT-HFD mice...
July 25, 2017: Oncotarget
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