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Tissue resident nk cell

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...
November 30, 2016: Science China. Life Sciences
Jonathan Merola, Daniel D Jane-Wit, Jordan S Pober
PURPOSE OF REVIEW: Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy. This review discusses recently reported mechanistic insights of allograft vasculopathy pathogenesis as well as recent clinical evaluations of new therapeutic approaches. RECENT FINDINGS: Although adaptive immunity is the major driver of allograft vasculopathy, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA)...
November 24, 2016: Current Opinion in Organ Transplantation
Bryan Simons, Maria E Ferrini, Sophia Carvalho, David J P Bassett, Zeina Jaffar, Kevan Roberts
In allergic asthma, inhalation of airborne allergens such as the house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI2 and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (i.e., PGI2 IP receptor-deficient [IP(-/-)]) were compared with wild type (WT) mice. Surprisingly, IP(-/-) mice had increased numbers of pulmonary CD3(-)NK1.1(+)Ly49b(+) NK cells producing IFN-γ that was inversely associated with the number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Rα and IL-13 compared with WT animals...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Joshua A Vieth, Joy Das, Fanomezana M Ranaivoson, Davide Comoletti, Lisa K Denzin, Derek B Sant'Angelo
The interaction between the T cell antigen receptor (TCR) expressed by natural killer T cells (NKT cells) and the antigen-presenting molecule CD1d is distinct from interactions between the TCR and major histocompatibility complex (MHC). Our molecular modeling suggested that a hydrophobic patch created after TCRα-TCRβ pairing has a role in maintaining the conformation of the NKT cell TCR. Disruption of this patch ablated recognition of CD1d by the NKT cell TCR but not interactions of the TCR with MHC. Partial disruption of the patch, while permissive to the recognition of CD1d, significantly altered NKT cell development, which resulted in the selective accumulation of adipose-tissue-resident NKT cells...
November 21, 2016: Nature Immunology
Yuhao Jiao, Nicholas D Huntington, Gabrielle T Belz, Cyril Seillet
Group 1 innate lymphoid cells (ILCs) comprise the natural killer (NK) cells and ILC1s that reside within peripheral tissues. Several different ILC1 subsets have recently been characterized; however, no unique markers have been identified that uniquely define these subsets. Whether ILC1s and NK cells are in fact distinct lineages, or alternately exhibit transitional molecular programs that allow them to adapt to different tissue niches remains an open question. NK cells are the prototypic member of the Group 1 ILCs and have been historically assigned the functions of what now appears to be a multi-subset family that are distributed throughout the body...
2016: Frontiers in Immunology
Miljana Radenkovic, Kristina Uvebrant, Oskar Skog, Luis Sarmiento, Jeanette Avartsson, Peter Storm, Petter Vickman, Per-Anders Bertilsson, Malin Fex, Olle Korsgren, Corrado M Cilio
The current view of type 1 diabetes (T1D) is that it is an immune-mediated disease where lymphocytes infiltrate the pancreatic islets, promote killing of beta cells and cause overt diabetes. Although tissue resident immune cells have been demonstrated in several organs, the composition of lymphocytes in human healthy pancreatic islets have been scarcely studied. Here we aimed to investigate the phenotype of immune cells associated to human islets of non-diabetic organ donors. A flow cytometry analysis of isolated islets from perfused pancreases (n=38) was employed to identify alpha, beta, T, NK and B cells...
October 26, 2016: Clinical and Experimental Immunology
June Ho Shin, Mikel D Haggadone, John B Sunwoo
The Distal-less (Dlx) homeobox transcription factors (TFs) play a prominent role in regulating multiple facets of vertebrate biology. Though widely studied as mediators of tissue development, recent work has uncovered a role for this TF family in modulating the vertebrate hematopoietic compartment. Pertinent to our study, murine Dlx1-3 are expressed in an innate lymphocyte population known as natural killer (NK) cells, and they are implicated to assume a functional role in the NK cell maturation pathway. However, Dlx target genes are poorly understood...
September 2016: Biochemistry and Biophysics Reports
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...
October 17, 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 natural killer (NK) cells in peripheral blood, relatively little is known about NK cells in the 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, chronic obstructive pulmonary disease, infections, and cancer. OBJECTIVE: We sought to analyze and compare the phenotypic and 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...
September 1, 2016: EMBO Molecular Medicine
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