CD69 is a direct HIF-1α target gene in hypoxia as a mechanism enhancing expression on tumor-infiltrating T lymphocytes

Oncoimmunology
Sara LabianoIgnacio Melero

Abstract

CD69 is an early activation marker on the surface of T lymphocytes undergoing activation by cognate antigen. We observed intense expression of CD69 on tumor-infiltrating T-lymphocytes that reside in the hypoxic tumor microenvironment and hypothesized that CD69 could be, at least partially, under the control of the transcriptional hypoxia response. In line with this, human and mouse CD3-stimulated lymphocytes cultured under hypoxia (1% O2) showed increased expression of CD69 at the protein and mRNA level. Consistent with these findings, mouse T lymphocytes that had recently undergone hypoxia in vivo, as denoted by pimonidazole staining, were more frequently CD69+ in the tumor and bone marrow hypoxic tissue compartments. We found evidence for HIF-1α involvement both when using T-lymphocytes from inducible HIF-1α-/- mice and when observing tumor-infiltrating T-lymphocytes in mice whose T cells are HIF-1α-/-. Direct pro-transcriptional activity of HIF-1α on a newly identified hypoxia response element (HRE) found in the human CD69 locus was demonstrated by ChIP experiments. These results uncover a connection between the HIF-1α oxygen-sensing pathway and CD69 immunobiology.

References

Oct 13, 2001·Science·R K Bruick, S L McKnight
Feb 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Hidefumi KojimaMichail V Sitkovsky
Oct 18, 2002·European Journal of Immunology·María del Carmen CastellanosManuel O de Landázuri
Feb 5, 2005·Blood·Enric EspluguesPilar Lauzurica
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hiroshi NakamuraHirotoshi Tanaka
Jul 12, 2005·The Journal of Clinical Investigation·Carole PeyssonnauxRandall S Johnson
Aug 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Akio OhtaMichail Sitkovsky
Aug 22, 2006·Journal of Leukocyte Biology·David SanchoFrancisco Sánchez-Madrid
Jan 24, 2009·Nature Reviews. Drug Discovery·Peter FraislPeter Carmeliet
May 14, 2010·The Journal of Biological Chemistry·Alexander J BankovichJason G Cyster
Jul 14, 2010·The Journal of Allergy and Clinical Immunology·Pilar MartínFrancisco Sánchez-Madrid
Sep 22, 2010·Circulation·Aranzazu Cruz-AdaliaPilar Martín
Mar 18, 2011·The Journal of Investigative Dermatology·Amalia LamanaGloria Martinez del Hoyo
Nov 2, 2011·Gynecologic Oncology·Wei-Ting HwangGeorge Coukos
Dec 31, 2011·International Immunology·Ai IkejiriShigeo Koyasu
Oct 1, 2013·Nature Immunology·Andrew L DoedensAnanda W Goldrath
Oct 29, 2013·Nature Immunology·Laura K MackayThomas Gebhardt
Apr 23, 2014·Molecular and Cellular Biology·Hortensia de la FuenteFrancisco Sánchez-Madrid
Apr 30, 2014·The Journal of Experimental Medicine·Muhammad Zaeem NomanSalem Chouaib
Jun 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Anna OkhrimenkoJun Dong
Jul 6, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yong-Chen LuPaul F Robbins
Nov 5, 2014·Immunity·Asis PalazonRandall S Johnson
Jan 28, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura K MackayThomas Gebhardt
Mar 15, 2015·Cancer Research·Patricia MaisoIrene M Ghobrial
May 13, 2015·Seminars in Oncology·Sara LabianoIgnacio Melero
Jun 30, 2015·Nature Medicine·Chang Ook Park, Thomas S Kupper
Aug 8, 2015·Clinical Biochemistry·Eberhard Wieland, Maria Shipkova
Aug 25, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chih-Ru LinShui-Tein Chen
Aug 25, 2015·Molecular Immunology·Anthony T Phan, Ananda W Goldrath
Jan 16, 2016·Molecular Aspects of Medicine·Eoin P CumminsCormac T Taylor
Jan 23, 2016·Molecular Aspects of Medicine·Mun Chiang ChanPeter J Ratcliffe
Apr 2, 2016·Inflammation·Zu-Cheng Yang, Yi Liu

❮ Previous
Next ❯

Citations

May 6, 2017·European Journal of Immunology·Danay Cibrián, Francisco Sánchez-Madrid
Oct 12, 2018·Biochemical Society Transactions·Abel AngMargreet C M Vissers
Nov 6, 2018·Frontiers in Immunology·David Schreiner, Carolyn G King
Jun 24, 2020·Biochemistry. Biokhimii︠a︡·L V KrechetovaN K Tetruashvili
Jul 1, 2019·Trends in Immunology·Simone L ParkLaura K Mackay
Mar 10, 2021·Cold Spring Harbor Perspectives in Biology·Feline E DijkgraafTon N M Schumacher

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
FACS
PCR
ChIP
Immunoprecipitation Assay

Software Mentioned

Imaris Bitplane
Prism
FlowJo ( Treestar )
Image J

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.