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Innate lymphoid cells liver

Hui Peng, Zhigang Tian
Nature killer (NK) cells are important lymphocytes of the innate immune system, well known for their pivotal roles in immune surveillance and defense against tumor and virus-infected cells. Current studies have revealed that NK cells are not a homogeneous population, but instead consist of distinct subsets with diverse characteristics. As an organ with predominant innate immunity, the liver is enriched with NK cells, among which two distinct NK cell subsets have recently been identified: conventional NK (cNK) cells and tissue-resident NK (trNK) cells...
December 2016: Science China. Life Sciences
Katrin Neumann, Khalil Karimi, Jana Meiners, Ruth Voetlause, Silja Steinmann, Werner Dammermann, Stefan Lüth, Farahnaz Asghari, Claudia Wegscheid, Andrea K Horst, Gisa Tiegs
Type 2 innate lymphoid cells (ILC2) mediate inflammatory immune responses in the context of diseases triggered by the alarmin IL-33. In recent years, IL-33 has been implicated in the pathogenesis of immune-mediated liver diseases. However, the immunoregulatory function of ILC2s in the inflamed liver remains elusive. Using the murine model of Con A-induced immune-mediated hepatitis, we showed that selective expansion of ILC2s in the liver was associated with highly elevated hepatic IL-33 expression, severe liver inflammation, and infiltration of eosinophils...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Dimitry A Chistiakov, Murry C Killingsworth, Veronika A Myasoedova, Alexander N Orekhov, Yuri V Bobryshev
CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells...
November 21, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Petya Apostolova, Robert Zeiser
Acute graft-versus-host disease (GvHD) causes high mortality in patients undergoing allogeneic hematopoietic cell transplantation. An early event in the classical pathogenesis of acute GvHD is tissue damage caused by the conditioning treatment or infection that consecutively leads to translocation of bacterial products [pathogen-associated molecular patterns (PAMPs)] into blood or lymphoid tissue, as well as danger-associated molecular patterns (DAMPs), mostly intracellular components that act as pro-inflammatory agents, once they are released into the extracellular space...
2016: Frontiers in Immunology
Xin Wei, Jiu-Ping Wang, Chun-Qiu Hao, Xiao-Fei Yang, Lin-Xu Wang, Chang-Xing Huang, Xue-Fan Bai, Jian-Qi Lian, Ye Zhang
The mechanism of hepatitis B virus (HBV) induced liver inflammation is not fully elucidated. Notch signaling augmented interleukin (IL)-22 secretion in CD4(+) T cells, and Notch-IL-22 axis fine-tuned inflammatory response. We previously demonstrated a proinflammatory role of IL-22 in HBV infection. Thus, in this study, we analyzed the role of Notch in development of IL-22-producing cells in HBV infection by inhibition of Notch signaling using γ-secretase inhibitor DAPT in both hydrodynamic induced HBV-infected mouse model and in peripheral blood cells isolated from patients with HBV infection...
2016: Frontiers in Cellular and Infection Microbiology
Ryuji Iida, Kaori Shinoda, Yuki Hayano, Yoshinori Nagai, Kiyoshi Takatsu, Taku Kouro
B-1 cells represent a sub-fraction of B lymphocytes that participate in T cell-independent antibody production and contribute to innate immunity. While the production of B-1 cells is favored during the fetal waves of lymphopoiesis, it has been unclear when and how that differentiation option is specified. To clarify this, lymphoid and hematopoietic progenitors of fetal liver (FL) and adult bone marrow (ABM) were examined for the B cell differentiation potential. Mouse common lymphoid progenitors (CLPs) and more primitive KSL fraction of FL and ABM were transferred to SCID mice and donor-derived B cell subsets were analyzed 4 weeks later...
2016: PloS One
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...
January 2017: 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...
December 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
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