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Tissue resident nk cell

Sofie Perdu, Barbara Castellana, Yoona Kim, Kathy Chan, Lauren DeLuca, Alexander G Beristain
Over one-fifth of North American women of childbearing age are obese, putting these women at risk for a variety of detrimental chronic diseases. In addition, obesity increases the risk for developing major complications during pregnancy. The mechanisms by which obesity contributes to pregnancy complications and loss remain unknown. Increasing evidence indicates that obesity results in major changes to adipose tissue immune cell composition and function; whether or not obesity also affects immune function in the uterus has not been explored...
July 21, 2016: JCI Insight
Luhua H Zhang, June Ho Shin, Mikel D Haggadone, John B Sunwoo
A tissue-resident population of natural killer cells (NK cells) in the liver has recently been described to have the unique capacity to confer immunological memory in the form of hapten-specific contact hypersensitivity independent of T and B cells. Factors regulating the development and maintenance of these liver-resident NK cells are poorly understood. The aryl hydrocarbon receptor (AhR) is a transcription factor modulated by exogenous and endogenous ligands that is important in the homeostasis of immune cells at barrier sites, such as the skin and gut...
September 26, 2016: Journal of Experimental Medicine
Nicole Marquardt, Eliisa Kekäläinen, Puran Chen, Egle Kvedaraite, Jennifer N Wilson, Martin A Ivarsson, Jenny Mjösberg, Lena Berglin, Jesper Säfholm, Martijn L Manson, Mikael Adner, Mamdoh Al-Ameri, Per Bergman, Ann-Charlotte Orre, Mattias Svensson, Barbro Dahlén, Sven-Erik Dahlén, Hans-Gustaf Ljunggren, Jakob Michaëlsson
BACKGROUND: In contrast to the extensive knowledge about human NK cells in peripheral blood, relatively little is known about NK cells in human lung. Knowledge about the composition, differentiation, and function of human lung NK cells is critical to better understand their role in diseases affecting the lung, including asthma, COPD, infections, and cancer. OBJECTIVE: We sought to analyze and compare the phenotypic as well as functional characteristics of NK cells in the human lung and peripheral blood at the single cell level...
September 23, 2016: Journal of Allergy and Clinical Immunology
Tsuyoshi Kiniwa, Yutaka Enomoto, Natsumi Terazawa, Ai Omi, Naoko Miyata, Kenji Ishiwata, Atsushi Miyajima
Natural killer (NK) cells are known to be activated by Th1-type cytokines, such as IL-2, -12, or -18, and they secrete a large amount of IFN-γ that accelerates Th1-type responses. However, the roles of NK cells in Th2-type responses have remained unclear. Because IL-4 acts as an initiator of Th2-type responses, we examined the characteristics of NK cells in mice overexpressing IL-4. In this study, we report that IL-4 overexpression induces distinctive characteristics of NK cells (B220(high)/CD11b(low)/IL-18Rα(low)), which are different from mature conventional NK (cNK) cells (B220(low)/CD11b(high)/IL-18Rα(high))...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Timothy K Erick, Courtney K Anderson, Emma C Reilly, Jack R Wands, Laurent Brossay
The submandibular salivary gland (SMG), a major site of persistent infection for many viruses, contains a large NK cell population. Using NFIL3-deficient mice, PLZF reporter/fate mapping mice, and mixed bone marrow chimeras, we identified two distinct populations of NK cells in the SMG. Although phenotypically unique, the main population relies on NFIL3, but not PLZF, for development and, therefore, is developmentally similar to the conventional NK cell subset. In contrast, we found that approximately one quarter of the SMG NK cells develop independently of NFIL3...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Liat Sorski, Lee Shaashua, Rivka Melamed, Pini Matzner, Shamgar Ben-Eliyahu
Marginating-hepatic (MH) leukocytes (leukocytes adhering to the sinusoids of the liver), were shown to exhibit unique composition and characteristics compared to leukocytes of other immune compartments. Specifically, evidence suggests a distinct pro- and anti-inflammatory profile of the MH-leukocyte population and higher cytotoxicity of liver-specific NK cells (namely, pit cells) compared to circulating or splenic immunocytes in both mice and rats. The method presented herein enables selective harvesting of MH leukocytes by forced perfusion of the liver in mice and rats...
2016: Journal of Visualized Experiments: JoVE
Timothy E O'Sullivan, Moritz Rapp, Xiying Fan, Orr-El Weizman, Priya Bhardwaj, Nicholas M Adams, Thierry Walzer, Andrew J Dannenberg, Joseph C Sun
Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency...
August 16, 2016: Immunity
Claude Lambert, Yuenv Wu, Carmen Aanei
Myelodysplastic syndrome (MDS) is characterized by an ineffective hematopoiesis with production of aberrant clones and a high cell apoptosis rate in bone marrow (BM). Macrophages are in charge of phagocytosis. Innate Immune cells and specific T cells are in charge of immunosurveillance. Little is known on BM cell recruitment and activity as BM aspirate is frequently contaminated with peripheral blood. But evidences suggest an active role of immune cells in protection against MDS and secondary leukemia. BM CD8(+) CD28(-) CD57(+) T cells are directly cytotoxic and have a distinct cytokine signature in MDS, producing TNF-α, IL-6, CCL3, CCL4, IL-1RA, TNFα, FAS-L, TRAIL, and so on...
2016: Frontiers in Oncology
Cathal Harmon, Mark W Robinson, Ronan Fahey, Sarah Whelan, Diarmaid D Houlihan, Justin Geoghegan, Cliona O'Farrelly
The adult human liver is enriched with natural killer (NK) cells, accounting for 30-50% of hepatic lymphocytes, which include tissue-resident hepatic NK-cell subpopulations, distinct from peripheral blood NK cells. In murine liver, a subset of liver-resident hepatic NK cells have altered expression of the two highly related T-box transcription factors, T-bet and eomesodermin (Eomes). Here, we investigate the heterogeneity of T-bet and Eomes expression in NK cells from healthy adult human liver with a view to identifying human liver-resident populations...
September 2016: European Journal of Immunology
Andrew L Doedens, Mark P Rubinstein, Emilie T Gross, J Adam Best, David H Craig, Megan K Baker, David J Cole, Jack D Bui, Ananda W Goldrath
Despite clinical potential and recent advances, durable immunotherapeutic ablation of solid tumors is not routinely achieved. IL15 expands natural killer cell (NK), natural killer T cell (NKT) and CD8(+) T-cell numbers and engages the cytotoxic program, and thus is under evaluation for potentiation of cancer immunotherapy. We found that short-term therapy with IL15 bound to soluble IL15 receptor α-Fc (IL15cx; a form of IL15 with increased half-life and activity) was ineffective in the treatment of autochthonous PyMT murine mammary tumors, despite abundant CD8(+) T-cell infiltration...
September 2, 2016: Cancer Immunology Research
Janine E Melsen, Gertjan Lugthart, Arjan C Lankester, Marco W Schilham
Two human natural killer (NK) cell subsets are usually distinguished, displaying the CD56(dim)CD16(+) and the CD56(bright)CD16(-/+) phenotype. This distinction is based on NK cells present in blood, where the CD56(dim) NK cells predominate. However, CD56(bright) NK cells outnumber CD56(dim) NK cells in the human body due to the fact that they are predominant in peripheral and lymphoid tissues. Interestingly, within the total CD56(bright) NK cell compartment, a major phenotypical and functional diversity is observed, as demonstrated by the discovery of tissue-resident CD56(bright) NK cells in the uterus, liver, and lymphoid tissues...
2016: Frontiers in Immunology
Enrico Lugli, Kelly Hudspeth, Alessandra Roberto, Domenico Mavilio
Efficient immune responses to invading pathogens are the result of the complex but coordinated synergy between a variety of cell types from both the innate and adaptive arms of the immune system. While adaptive and innate immune responses are highly complementary, some cells types within these two systems perform similar functions, underscoring the need for redundancy and increased flexibility. In this review, we will discuss the striking shared features of immunological memory and tissue residency recently discovered between T cells, a component of the adaptive immune system, and natural killer (NK) cells, members generally assigned to the innate compartment...
August 2016: European Journal of Immunology
Francesca Mingozzi, Roberto Spreafico, Tatiana Gorletta, Clara Cigni, Marco Di Gioia, Michele Caccia, Laura Sironi, Maddalena Collini, Matias Soncini, Michela Rusconi, Ulrich H von Andrian, Giuseppe Chirico, Ivan Zanoni, Francesca Granucci
Natural killer (NK) cells are critical players against tumors. The outcome of anti-tumor vaccination protocols depends on the efficiency of NK-cell activation, and efforts are constantly made to manipulate them for immunotherapeutic approaches. Thus, a better understanding of NK-cell activation dynamics is needed. NK-cell interactions with accessory cells and trafficking between secondary lymphoid organs and tumoral tissues remain poorly characterized. Here, we show that upon triggering innate immunity with lipopolysaccharide (LPS), NK cells are transiently activated, leave the lymph node, and infiltrate the tumor, delaying its growth...
2016: EMBO Molecular Medicine
Kerstin A Stegmann, Francis Robertson, Navjyot Hansi, Upkar Gill, Celeste Pallant, Theodoros Christophides, Laura J Pallett, Dimitra Peppa, Claire Dunn, Giuseppe Fusai, Victoria Male, Brian R Davidson, Patrick Kennedy, Mala K Maini
Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p < 0.0001). Human hepatic CXCR6+ NK had an immature phenotype (predominantly CD56(bright)CD16-CD57-), and expressed the tissue-residency marker CD69. CXCR6+ NK produced fewer cytotoxic mediators and pro-inflammatory cytokines than the non-liver-specific CXCR6- fraction...
2016: Scientific Reports
Emily R Levy, Mattias Carlsten, Richard W Childs
The ability of natural killer (NK) cells to mediate antitumor effects following adoptive transfer is dependent on their capacity to traffic to the microenvironment where tumors reside. Recent studies have shown that cytokine-activated and ex vivo-expanded NK cells lack or express at low levels homing receptors required to achieve tissue-specific tumor targeting by cells administered intravenously. In this chapter, we describe a method to enhance NK cell homing toward specific chemoattractants expressed in secondary lymphoid tissues through genetic modification of NK cells using mRNA electroporation...
2016: Methods in Molecular Biology
Isabel E Ishizuka, Michael G Constantinides, Herman Gudjonson, Albert Bendelac
The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. We discuss the identification of a common innate lymphoid cell precursor characterized by transient expression of the transcription factor PLZF, and the lineage relationships of innate lymphoid cells with conventional natural killer cells and lymphoid tissue inducer cells...
May 20, 2016: Annual Review of Immunology
Hannah M Cheeseman, Ann M Carias, Abbey B Evans, Natalia J Olejniczak, Paul Ziprin, Deborah F L King, Thomas J Hope, Robin J Shattock
The majority of new Human Immunodeficiency Virus (HIV)-1 infections are acquired via sexual transmission at mucosal surfaces. Partial efficacy (31.2%) of the Thai RV144 HIV-1 vaccine trial has been correlated with Antibody-dependent Cellular Cytotoxicity (ADCC) mediated by non-neutralizing antibodies targeting the V1V2 region of the HIV-1 envelope. This has led to speculation that ADCC and other antibody-dependent cellular effector functions might provide an important defense against mucosal acquisition of HIV-1 infection...
2016: PloS One
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
Jingjing Jiao, Kohtaro Ooka, Holger Fey, Maria Isabel Fiel, Adeeb H Rahmman, Kensuke Kojima, Yujin Hoshida, Xintong Chen, Tatiana de Paula, Diana Vetter, David Sastre, Ka Hin Lee, Youngmin A Lee, Meena Bansal, Scott L Friedman, Miriam Merad, Costica Aloman
BACKGROUND & AIMS: Interleukin-15 (IL-15) and its high affinity receptor interleukin-15 receptor alpha (IL-15Rα) are widely expressed in immune cells and hepatic resident cells. IL-15 signaling has important functions in homeostasis of natural killer (NK), natural killer T (NKT) and cytotoxic T (CD8(+) T) cells, and in liver regeneration. We hypothesized that IL-15 has a protective role in liver fibrosis progression by maintaining NK cell homeostasis. METHODS: Fibrosis was induced using two mechanistically distinct models...
August 2016: Journal of Hepatology
Ines G Harper, Jason M Ali, Simon J F Harper, Elizabeth Wlodek, Jawaher Alsughayyir, Margaret C Negus, M Saeed Qureshi, Reza Motalleb-Zadeh, Kourosh Saeb-Parsy, Eleanor M Bolton, J Andrew Bradley, Menna R Clatworthy, Thomas M Conlon, Gavin J Pettigrew
Chronic rejection of solid organ allografts remains the major cause of transplant failure. Donor-derived tissue-resident lymphocytes are transferred to the recipient during transplantation, but their impact on alloimmunity is unknown. Using mouse cardiac transplant models, we show that graft-versus-host recognition by passenger donor CD4 T cells markedly augments recipient cellular and humoral alloimmunity, resulting in more severe allograft vasculopathy and early graft failure. This augmentation is enhanced when donors were pre-sensitized to the recipient, is dependent upon avoidance of host NK cell recognition, and is partly due to provision of cognate help for allo-specific B cells from donor CD4 T cells recognizing B cell MHC class II in a peptide-degenerate manner...
May 10, 2016: Cell Reports
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