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Aline Van Acker, Konrad Gronke, Aindrila Biswas, Liesbet Martens, Yvan Saeys, Jessica Filtjens, Sylvie Taveirne, Els Van Ammel, Tessa Kerre, Patrick Matthys, Tom Taghon, Bart Vandekerckhove, Jean Plum, Ildiko Rita Dunay, Andreas Diefenbach, Georges Leclercq
The Ly49E receptor is preferentially expressed on murine innate-like lymphocytes, such as epidermal Vγ3 T cells, intestinal intraepithelial CD8αα(+) T lymphocytes, and CD49a(+) liver natural killer (NK) cells. As the latter have recently been shown to be distinct from conventional NK cells and have innate lymphoid cell type 1 (ILC1) properties, we investigated Ly49E expression on intestinal ILC populations. Here, we show that Ly49E expression is very low on known ILC populations, but it can be used to define a previously unrecognized intraepithelial innate lymphoid population...
May 16, 2017: Cell Reports
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 21, 2017: Immunity
Tingting Li, Jian Wang, Yanshi Wang, Yongyan Chen, Haiming Wei, Rui Sun, Zhigang Tian
Although NK cells are classified as innate immune cells, recent studies have demonstrated the transformation of NK cells into long-lived memory cells that contribute to secondary immune responses in certain mouse models. However, whether NK cells mount an Ag-specific memory response to acute influenza virus infection has not yet been examined. Here, we show that, consistent with previous studies, lung NK cells play an important role in controlling viral proliferation after primary influenza virus infection...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Valeria Sordi, Anna Ferri, Valentina Ceserani, Emilio Ciusani, Erica Dugnani, Silvia Pellegrini, Rita Nano, Lorenza Pecciarini, Augusto Pessina, Luisa Pascucci, Lorenzo Piemonti, Giulio Alessandri
BACKGROUND: In vitro primary cultures of microvascular endothelial cells from endocrine pancreas are difficult to obtain, but can be a very helpful tool for studies of islet biology, transplantation and regenerative medicine. METHODS: We applied a protocol recently described for the isolation and culture of brain microvascular endothelial cells (EC) on human pancreatic islets. EC obtained were characterized in terms of morphological (light and transmission electron microscopy), phenotypical (by immunofluorescence and flow cytometry) and functional (cord formation assay and protein secretion by multiplex bead-based assay) characteristics...
January 2017: Cytotherapy
Abhishek Harichandan, Kavitha Sivasubramaniyan, Jörg Hennenlotter, Sven Poths, Jens Bedke, Stephan Kruck, Arnulf Stenzl, Hans-Jörg Bühring
In-depth understanding of human spermatogenesis requires studying specific molecular signatures and interactions of spermatogonia with other testicular cell populations, for which isolation of pure populations of different cell types is crucial. Here, we describe a technique to simultaneously enrich pure, multiple testicular cell populations, including spermatogonia, endothelial (TECs), and perivascular mesenchymal stem/stromal cells (TMSCs), from testicular tissue by flow cytometry using a combination of defined markers...
February 15, 2017: Stem Cells and Development
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
Rodney Macedo, Juliette Rochefort, Maude Guillot-Delost, Kae Tanaka, Aline Le Moignic, Clara Noizat, Claude Baillou, Véronique Mateo, Antoine F Carpentier, Eric Tartour, Chloé Bertolus, Bertrand Bellier, Géraldine Lescaille, François M Lemoine
Despite current therapy, head and neck squamous cell carcinomas (HNSCCs) arising from various mucosal sites of the upper aero-digestive tract frequently relapse in a loco-regional manner and have a poor prognosis. Our objective was to validate an innovative mucosal route of vaccination using plasmo virus-like particles (pVLPs) in a pre-clinical orthotopic model of HNSCCs. For this purpose, we used pVLP-E7, that are plasmid DNA encoding retroviral virus-like particles carrying a truncated E7 oncoprotein from HPV-16 as antigen model, to vaccinate mice bearing pre-established TC-1 tumors implanted into the buccal mucosa...
July 2016: Oncoimmunology
Ryuichi Totsuka, Takaaki Kondo, Shigeki Matsubara, Midori Hirai, Yoichi Kurebayashi
VLA-1 (very late antigen-1) is implicated in recruitment, retention and activation of leukocytes and its blockade has been referred as a potential target of new drug discovery to address unmet medical needs in inflammatory disease area. In the present study, we investigate the effects of an anti-murine CD49a (integrin α subunit of VLA-1) monoclonal antibody (Ha31/8) on various experimental models of inflammatory diseases in mice. Pretreatment with Ha31/8 at an intraperitoneal dose of 250 µg significantly (P<0...
July 5, 2016: Kobe Journal of Medical Sciences
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
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
Meijuan Zheng, Rui Sun, Haiming Wei, Zhigang Tian
Although recent clinical studies demonstrate that NK cell function is impaired in hepatitis B virus (HBV)-persistent patients, whether or how NK cells play a role in anti-HBV adaptive immunity remains to be explored. Using a mouse model mimicking acute HBV infection by hydrodynamic injection of an HBV plasmid, we observed that although serum hepatitis B surface Ag and hepatitis B envelope Ag were eliminated within 3 to 4 wk, HBV might persist for >8 wk in CD8(-/-) mice and that adoptive transfer of anti-HBV CD8(+) T cells restored the ability to clear HBV in HBV-carrier Rag1(-/-) mice...
May 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Thomas Verrier, Naoko Satoh-Takayama, Nicolas Serafini, Solenne Marie, James P Di Santo, Christian A J Vosshenrich
Group 3 innate lymphoid cells (ILC3) actively participate in mucosal defense and homeostasis through prompt secretion of IL-17A, IL-22, and IFN-γ. Reports identify two ILC3 lineages: a CCR6(+)T-bet(-) subset that appears early in embryonic development and promotes lymphoid organogenesis and a CCR6(-)T-bet(+) subset that emerges after microbial colonization and harbors NKp46(+) ILC3. We demonstrate that NKp46 expression in the ILC3 subset is highly unstable. Cell fate mapping using Ncr1(CreGFP) × Rosa26(RFP) mice revealed the existence of an intestinal RFP(+) ILC3 subset (Ncr1(FM)) lacking NKp46 expression at the transcript and protein levels...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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
Lukasz Bialkowski, Alexia van Weijnen, Kevin Van der Jeught, Dries Renmans, Lidia Daszkiewicz, Carlo Heirman, Geert Stangé, Karine Breckpot, Joeri L Aerts, Kris Thielemans
The lack of appropriate mouse models is likely one of the reasons of a limited translational success rate of therapeutic vaccines against cervical cancer, as rapidly growing ectopic tumours are commonly used for preclinical studies. In this work, we demonstrate that the tumour microenvironment of TC-1 tumours differs significantly depending on the anatomical location of tumour lesions (i.e. subcutaneously, in the lungs and in the genital tract). Our data demonstrate that E7-TriMix mRNA vaccine-induced CD8(+) T lymphocytes migrate into the tumour nest and control tumour growth, although they do not express mucosa-associated markers such as CD103 or CD49a...
March 2, 2016: Scientific Reports
Selma Boulenouar, Jean-Marc Doisne, Amanda Sferruzzi-Perri, Louise M Gaynor, Jens Kieckbusch, Elisa Balmas, Hong Wa Yung, Shagayegh Javadzadeh, Léa Volmer, Delia A Hawkes, Keli Phillips, Hugh J M Brady, Abigail L Fowden, Graham J Burton, Ashley Moffett, Francesco Colucci
Uterine NK cells are innate lymphoid cells (ILC) that populate the uterus and expand during pregnancy, regulating placental development and fetal growth in humans and mice. We have recently characterized the composition of uterine ILCs (uILCs), some of which require the transcription factor NFIL3, but the extent to which NFIL3-dependent cells support successful reproduction in mice is unknown. By mating Nfil3 (-/-) females with wild-type males, here we show the effects of NFIL3 deficiency in maternal cells on both the changes in uILCs during pregnancy and the downstream consequences on reproduction...
2016: Frontiers in Immunology
Saïda Dadi, Sagar Chhangawala, Benjamin M Whitlock, Ruth A Franklin, Chong T Luo, Soyoung A Oh, Ahmed Toure, Yuri Pritykin, Morgan Huse, Christina S Leslie, Ming O Li
Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remains obscure. Here, we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, T cell receptor (TCR)αβ, and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1...
January 28, 2016: Cell
Felix Scholz, Shruti Naik, Fayyaz S Sutterwala, Daniel H Kaplan
No abstract text is available yet for this article.
December 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Theresa Hydes, Mohammed Abuhilal, Thomas Armstrong, John Primrose, Arjun Takhar, Salim Khakoo
BACKGROUND: Selected populations of murine natural killer (NK) cells possess memory features to haptens, cytokines, and viruses. Liver-specific adhesion molecules CXCR6 and CD49a have been identified as surface markers in mice. In people, expansion of long-lived terminally differentiated NKG2C+ populations occur in the blood after viral infection. We aimed to compare intrahepatic and blood NK cell receptor expression to determine the existence of CD49a+ and CXCR6+ NK cells in human liver and define the maturation status of NKG2C+ NK cells at this site...
February 26, 2015: Lancet
Felix Scholz, Shruti Naik, Fayyaz S Sutterwala, Daniel H Kaplan
Recruitment of innate immune effector cells into sites of infection is a critical component of resistance to pathogen infection. Using a model of intradermal footpad injection of Candida albicans, we observed that inflammation as measured by footpad thickness and neutrophil recruitment occurred independent of adoptive immunity but was significantly reduced in MyD88(-/-) and IL-6(-/-) mice. Unexpectedly, huLangerin-DTA mice (ΔLC) that lack Langerhans cells (LC) developed increased skin inflammation and expressed higher amounts of IL-6, suggesting a suppressive role for LC...
September 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Graham G Walmsley, David A Atashroo, Zeshaan N Maan, Michael S Hu, Elizabeth R Zielins, Jonathan M Tsai, Dominik Duscher, Kevin Paik, Ruth Tevlin, Owen Marecic, Derrick C Wan, Geoffrey C Gurtner, Michael T Longaker
Adipose tissue contains an abundant source of multipotent mesenchymal cells termed "adipose-derived stromal cells" (ASCs) that hold potential for regenerative medicine. However, the heterogeneity inherent to ASCs harvested using standard methodologies remains largely undefined, particularly in regards to differences across donors. Identifying the subpopulations of ASCs predisposed toward differentiation along distinct lineages holds value for improving graft survival, predictability, and efficiency. Human ASCs (hASCs) from three different donors were independently isolated by density-based centrifugation from adipose tissue and maintained in culture or differentiated along either adipogenic or osteogenic lineages using differentiation media...
August 2015: Tissue Engineering. Part A
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