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Innate lymphoid cells liver

Marie Marotel, Uzma Hasan, Sébastien Viel, Antoine Marçais, Thierry Walzer
Recent studies of immune populations in nonlymphoid organs have highlighted the great diversity of the innate lymphoid system. It has also become apparent that mouse and human innate lymphoid cells (ILCs) have distinct phenotypes and properties. In this issue of the European Journal of Immunology, Harmon et al. [Eur. J. Immunol. 2016. 46: 2111-2120] characterized human hepatic NK-cell subsets. The authors report that hepatic CD56(bright) NK cells resemble mouse liver ILC1s in that they express CXCR6 and have an immature phenotype...
September 2016: European Journal of Immunology
Peter D Krueger, Sowmya Narayanan, Fionna A Surette, Michael G Brown, Sun-Sang J Sung, Young S Hahn
The liver contains 2 transcriptionally distinct group 1 ILC subsets: CD49a(+) ILC1s and CD49b(+) NK cells. However, little is known about how group 1 ILCs contribute to hepatic immune responses. Therefore, we characterized murine liver-resident group 1 ILCs and found that CD49a(+) ILC1s express high levels of the inhibitory receptor NKG2A and localize near DCs in perivascular spaces surrounding the portal triads. Upon hepatic viral infection, NKG2A signaling in group 1 ILCs, especially in CD49a(+) ILC1s, inhibits CXCL9 expression required for robust accumulation of IFN-γ(+)CD49b(+) NK cells...
August 4, 2016: Journal of Leukocyte Biology
Konrad Gronke, Michael Kofoed-Nielsen, Andreas Diefenbach
Innate lymphoid cells (ILC) have only recently been recognized as a separate entity of the lymphoid lineage. Their subpopulations share common characteristics in terms of early development and major transcriptional circuitry with their related cousins of the T cell world. It is currently hypothesized that ILCs constitute an evolutionary older version of the lymphoid immune system. They are found at all primary entry points for pathogens such as mucosal surfaces of the lung and gastrointestinal system, the skin and the liver, which is the central contact point for pathogens that breach the intestinal barrier and enter the circulation...
July 6, 2016: Immunology Letters
Giovanni C Actis, Rinaldo Pellicano
The inflammatory bowel diseases (IBDs) are being seen as a gut inflammatory hub occurring: 1) with inflammatory spots in the eyes, skin, liver, joints (extra-intestinal manifestations); 2) with functionally contiguous disorders such as psoriasis and lung disease (barrier organ diseases); 3) as the consequence of genetic loss of non-redundant cell functions that are critical for gut homeostasis and defense (monogenic IBD). Recent multidisciplinary analysis, fostered by the input of genomic search, has helped hypothesize two pathogenetic models for the main phenotypes of IBDs...
June 17, 2016: Minerva Medica
Victor S Cortez, Luisa Cervantes-Barragan, Michelle L Robinette, Jennifer K Bando, Yaming Wang, Theresa L Geiger, Susan Gilfillan, Anja Fuchs, Eric Vivier, Joe C Sun, Marina Cella, Marco Colonna
The signals guiding differentiation of innate lymphoid cells (ILCs) within tissues are not well understood. Salivary gland (SG) ILCs as well as liver and intestinal intraepithelial ILC1 have markers that denote tissue residency and transforming growth factor-β (TGF-β) imprinting. We deleted Tgfbr2 in cells expressing the ILC and NK marker NKp46 and found that SG ILCs were reduced in number. They lost distinct tissue markers, such as CD49a, and the effector molecules TRAIL and CD73. Expression of the transcription factor Eomes, which promotes NK cell differentiation, was elevated...
May 17, 2016: Immunity
Kevin M Vannella, Thirumalai R Ramalingam, Lee A Borthwick, Luke Barron, Kevin M Hart, Robert W Thompson, Kristen N Kindrachuk, Allen W Cheever, Sandra White, Alison L Budelsky, Michael R Comeau, Dirk E Smith, Thomas A Wynn
Thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), and IL-33 are important initiators of type 2-associated mucosal inflammation and immunity. However, their role in the maintenance of progressive type 2 inflammation and fibrosis is much less clear. Using chronic models of helminth infection and allergic lung inflammation, we show that collective disruption of TSLP, IL-25, and IL-33 signaling suppresses chronic and progressive type 2 cytokine-driven inflammation and fibrosis. In a schistosome lung granuloma model or during chronic Schistosoma mansoni infection in the liver, individual ablation of TSLP, IL-25, or IL-33/ST2 had no impact on the development of IL-4/IL-13-dependent inflammation or fibrosis...
May 4, 2016: Science Translational Medicine
Percy A Knolle, Dirk Wohlleber
Liver sinusoidal endothelial cells (LSECs) line the liver sinusoids and separate passenger leukocytes in the sinusoidal lumen from hepatocytes. LSECs further act as a platform for adhesion of various liver-resident immune cell populations such as Kupffer cells, innate lymphoid cells or liver dendritic cells. In addition to having an extraordinary scavenger function, LSECs possess potent immune functions, serving as sentinel cells to detect microbial infection through pattern recognition receptor activation and as antigen (cross)-presenting cells...
May 2016: Cellular & Molecular Immunology
Raffaella Fontana, Aida Paniccia, Vincenzo Russo
There is growing evidence highlighting the ability of nuclear receptors to control not only metabolism, but also inflammation and cancer progression. In particular liver X receptors (LXRs), the nuclear receptors physiologically involved in cholesterol homeostasis, have been shown to regulate innate and adaptive immune responses in many pathological conditions, including cancer.We have recently demonstrated that LXR ligands (oxysterols) released by tumor cells may have an immunomodulatory role, affecting the immune cells involved in the antitumor immune response...
2016: Methods in Molecular Biology
Elisa Montaldo, Paola Vacca, Laura Chiossone, Daniele Croxatto, Fabrizio Loiacono, Stefania Martini, Simone Ferrero, Thierry Walzer, Lorenzo Moretta, Maria Cristina Mingari
Decidual and uterine natural killer (NK) cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent "cytotoxic" group 1 innate lymphoid cells (ILCs) and are distinct from the recently described "helper" ILC1. Here, we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and decidua express Eomesodermin (Eomes), thus suggesting that they are developmentally related to conventional NK cells. However, they differ from peripheral NK cells...
2015: Frontiers in Immunology
Frank Fasbender, Agata Widera, Jan G Hengstler, Carsten Watzl
In the 40 years since the discovery of natural killer (NK) cells, it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue-resident NK cells with distinct phenotypical and functional characteristics have been identified...
2016: Frontiers in Immunology
Ramesh Kudira, Thomas Malinka, Andreas Kohler, Michel Dosch, Mercedes Gomez de Agüero, Nicolas Melin, Stefanie Haegele, Patrick Starlinger, Niran Maharjan, Smita Saxena, Adrian Keogh, Deborah Stroka, Daniel Candinas, Guido Beldi
UNLABELLED: Paracrine signalling mediated by cytokine secretion is essential for liver regeneration after hepatic resection, yet the mechanisms of cellular crosstalk between immune and parenchymal cells are still elusive. Interleukin-22 (IL-22) is released by immune cells and mediates strong hepatoprotective functions. However, it remains unclear whether IL-22 is critical for the crosstalk between liver lymphocytes and parenchymal cells during liver regeneration after partial hepatectomy (PH)...
June 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Anne Baerenwaldt, Nicole von Burg, Matthias Kreuzaler, Selina Sitte, Edit Horvath, Annick Peter, David Voehringer, Antonius G Rolink, Daniela Finke
Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches...
March 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Isabel E Ishizuka, Sylvestre Chea, Herman Gudjonson, Michael G Constantinides, Aaron R Dinner, Albert Bendelac, Rachel Golub
The precise lineage relationship between innate lymphoid cells (ILCs) and lymphoid tissue-inducer (LTi) cells is poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and found that its bifurcation was marked by differential induction of the transcription factors PLZF and TCF1. Acquisition of individual effector programs specific to the ILC subsets ILC1, ILC2 and ILC3 was initiated later, at the common ILC precursor stage, by transient expression of mixed ILC1, ILC2 and ILC3 transcriptional patterns, whereas, in contrast, the development of LTi cells did not go through multilineage priming...
March 2016: Nature Immunology
Catherine J Andersen, Kelsey E Murphy, Maria Luz Fernandez
Obesity is associated with metabolic disturbances that cause tissue stress and dysfunction. Obese individuals are at a greater risk for chronic disease and often present with clinical parameters of metabolic syndrome (MetS), insulin resistance, and systemic markers of chronic low-grade inflammation. It has been well established that cells of the immune system play an important role in the pathogenesis of obesity- and MetS-related chronic diseases, as evidenced by leukocyte activation and dysfunction in metabolic tissues such as adipose tissue, liver, pancreas, and the vasculature...
January 2016: Advances in Nutrition
Felix Heymann, Frank Tacke
The liver is a central immunological organ with a high exposure to circulating antigens and endotoxins from the gut microbiota, particularly enriched for innate immune cells (macrophages, innate lymphoid cells, mucosal-associated invariant T (MAIT) cells). In homeostasis, many mechanisms ensure suppression of immune responses, resulting in tolerance. Tolerance is also relevant for chronic persistence of hepatotropic viruses or allograft acceptance after liver transplantation. The liver can rapidly activate immunity in response to infections or tissue damage...
February 2016: Nature Reviews. Gastroenterology & Hepatology
Denise E Lackey, Jerrold M Olefsky
Low-grade tissue inflammation induced by obesity can result in insulin resistance, which in turn is a key cause of type 2 diabetes mellitus. Cells of the innate immune system produce cytokines and other factors that impair insulin signalling, which contributes to the connection between obesity and the onset of type 2 diabetes mellitus. Here, we review the innate immune cells involved in secreting inflammatory factors in the obese state. In the adipose tissue, these cells include proinflammatory adipose tissue macrophages and natural killer cells...
January 2016: Nature Reviews. Endocrinology
Hiroko Tsutsui, Xianbin Cai, Shuhei Hayashi
The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra), and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation...
2015: Mediators of Inflammation
Shlomi Finkin, Detian Yuan, Ilan Stein, Koji Taniguchi, Achim Weber, Kristian Unger, Jeffrey L Browning, Nicolas Goossens, Shigeki Nakagawa, Ganesh Gunasekaran, Myron E Schwartz, Masahiro Kobayashi, Hiromitsu Kumada, Michael Berger, Orit Pappo, Klaus Rajewsky, Yujin Hoshida, Michael Karin, Mathias Heikenwalder, Yinon Ben-Neriah, Eli Pikarsky
Ectopic lymphoid-like structures (ELSs) are often observed in cancer, yet their function is obscure. Although ELSs signify good prognosis in certain malignancies, we found that hepatic ELSs indicated poor prognosis for hepatocellular carcinoma (HCC). We studied an HCC mouse model that displayed abundant ELSs and found that they constituted immunopathological microniches wherein malignant hepatocyte progenitor cells appeared and thrived in a complex cellular and cytokine milieu until gaining self-sufficiency...
December 2015: Nature Immunology
Sylvestre Chea, Cécilie Possot, Thibaut Perchet, Maxime Petit, Ana Cumano, Rachel Golub
Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2(-/-) Cxcr6(Gfp/+) reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation...
2015: Mediators of Inflammation
Daniel Engelbertsen, Amanda C Foks, Noah Alberts-Grill, Felicia Kuperwaser, Tao Chen, James A Lederer, Petr Jarolim, Nir Grabie, Andrew H Lichtman
OBJECTIVE: Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. APPROACH AND RESULTS: We demonstrate that CD25(+) ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr(-/-)rag1(-/-) mice...
December 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
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