Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function

Immunity
Heinrich SchlumsYenan T Bryceson

Abstract

The mechanisms underlying human natural killer (NK) cell phenotypic and functional heterogeneity are unknown. Here, we describe the emergence of diverse subsets of human NK cells selectively lacking expression of signaling proteins after human cytomegalovirus (HCMV) infection. The absence of B and myeloid cell-related signaling protein expression in these NK cell subsets correlated with promoter DNA hypermethylation. Genome-wide DNA methylation patterns were strikingly similar between HCMV-associated adaptive NK cells and cytotoxic effector T cells but differed from those of canonical NK cells. Functional interrogation demonstrated altered cytokine responsiveness in adaptive NK cells that was linked to reduced expression of the transcription factor PLZF. Furthermore, subsets of adaptive NK cells demonstrated significantly reduced functional responses to activated autologous T cells. The present results uncover a spectrum of epigenetically unique adaptive NK cell subsets that diversify in response to viral infection and have distinct functional capabilities compared to canonical NK cell subsets.

References

Jun 29, 1989·The New England Journal of Medicine·C A BironJ L Sullivan
Jul 1, 1988·Reviews of Infectious Diseases·A H Rook
Jan 28, 1994·Cell·A Weiss, D R Littman
Jul 16, 1993·Cell·W KolanusB Seed
Aug 12, 2004·Blood·Mónica GumáMiguel López-Botet
Aug 12, 2006·Immunity·Nicolas AnfossiEric Vivier
Nov 15, 2006·Immunological Reviews·Yenan T BrycesonEric O Long
Apr 1, 2008·The Journal of Biological Chemistry·Yu OikawaMasashi Kawaichi
Jul 25, 2008·Blood·Michael A Caligiuri
Jul 25, 2008·Blood·Taco W KuijpersEddy Roosnek
Jan 8, 2011·Science·Eric VivierSophie Ugolini
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sandra Lopez-VergèsLewis L Lanier
Aug 21, 2012·Nature Immunology·Natalie A BezmanUNKNOWN Immunological Genome Project Consortium
Dec 26, 2012·Frontiers in Immunology·Michael GleimerTaras Kreslavsky
Mar 2, 2013·Frontiers in Immunology·Frank CichockiYenan T Bryceson
Mar 16, 2013·Science·Veit R BuchholzDirk H Busch
Mar 16, 2013·Science·Carmen GerlachTon N M Schumacher
Mar 23, 2013·Annual Review of Immunology·Eric O LongSumati Rajagopalan
Apr 9, 2013·Bone Marrow Transplantation·S ItoA J Barrett
Nov 28, 2013·The Journal of Experimental Medicine·Matthew A FirthJoseph C Sun
Feb 11, 2014·Nature·Michael G ConstantinidesAlbert Bendelac
Jun 10, 2014·Immunity·Haifeng C XuPhilipp A Lang

❮ Previous
Next ❯

Citations

Nov 23, 2015·Current Opinion in Virology·Stephen N WaggonerCarolyn E Rydyznski
Feb 13, 2016·Trends in Immunology·Alexander Rölle, Petter Brodin
Jan 26, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Monzr M Al MalkiStefan O Ciurea
Feb 3, 2016·Nature Reviews. Immunology·Donna L FarberRolf M Zinkernagel
Jan 26, 2016·Nature Reviews. Immunology·Adelheid Cerwenka, Lewis L Lanier
Nov 22, 2015·Science China. Life Sciences·Yang LiXi Wang
Dec 20, 2015·Current Opinion in Immunology·Ning Wu, André Veillette
Mar 15, 2016·Frontiers in Immunology·Dara M Strauss-Albee, Catherine A Blish
Sep 19, 2015·Scandinavian Journal of Immunology·Teilah Kathryn HuthSonya Marshall-Gradisnik
Jul 25, 2015·Current Opinion in Virology·Berislav LisnićStipan Jonjić
Nov 26, 2015·Molecular Oncology·Lisa L LiuKarl-Johan Malmberg
Nov 26, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Matthias Voss, Yenan T Bryceson
Dec 1, 2015·Frontiers in Immunology·Mariella Della ChiesaAlessandro Moretta
Oct 27, 2015·Frontiers in Immunology·Vivien BéziatKarl-Johan Malmberg
Mar 12, 2016·Epigenetics : Official Journal of the DNA Methylation Society·John K WienckeKarl T Kelsey
Dec 19, 2015·Cellular and Molecular Gastroenterology and Hepatology·Barbara Rehermann
Mar 25, 2016·Médecine sciences : M/S·Thierry Walzer, Antoine Marçais
Aug 19, 2015·Immunological Reviews·Jodie P GoodridgeKarl-Johan Malmberg
Aug 19, 2015·Immunological Reviews·Nadir KadriPetter Höglund
Aug 15, 2015·Trends in Immunology·Carolyn E Rydyznski, Stephen N Waggoner
Jul 21, 2015·Nature Immunology·R Keith ReevesDan H Barouch
Apr 15, 2016·Viruses·Yi MaErsheng Kuang
Jun 19, 2015·Nature Immunology·Mihai G NeteaLuke A J O'Neill
Apr 20, 2016·Nature Immunology·Sammy BedouiWolfgang Kastenmüller
Apr 23, 2016·Science·Mihai G NeteaRamnik J Xavier
Apr 29, 2016·Nature Reviews. Immunology·Niklas K BjörkströmJakob Michaëlsson
May 10, 2016·Journal of Autoimmunity·Alice LaroniAntonio Uccelli
May 11, 2016·Trends in Immunology·Bianca TesiYenan T Bryceson
May 10, 2016·Nature Reviews. Immunology·Helen S GoodridgeChristopher B Wilson
Oct 22, 2015·Immunity·Timothy E O'SullivanLewis L Lanier
Jun 29, 2016·Mechanisms of Ageing and Development·Miguel López-BotetAldi Pupuleku
Jun 30, 2016·Seminars in Immunology·Tim D Holmes, Yenan T Bryceson
May 22, 2016·Blood·Rupert HandgretingerMaya C André
Aug 16, 2016·Human Immunology·Magdalena SipsGalit Alter
Jul 20, 2016·European Journal of Immunology·Enrico LugliDomenico Mavilio
Aug 30, 2016·The Journal of Clinical Investigation·Vanessa LandtwingChristian Münz
Sep 14, 2016·Frontiers in Immunology·Obinna ChijiokeChristian Münz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.