Treatment of HIV-Infected Individuals with the Histone Deacetylase Inhibitor Panobinostat Results in Increased Numbers of Regulatory T Cells and Limits Ex Vivo Lipopolysaccharide-Induced Inflammatory Responses

MSphere
Christel Rothe BrinkmannMartin Tolstrup

Abstract

Histone deacetylase inhibitors (HDACi) modulate the transcriptional activity of all cells, including innate and adaptive immune cells. Therefore, we aimed to evaluate immunological effects of treatment with the HDACi panobinostat in HIV-infected patients during a clinical phase IIa latency reversal trial. Using flow cytometry, we investigated changes in T cell activation (CD69, CD38, HLA-DR) and the expression of CD39 and CTLA4 on regulatory T cells (Tregs). Whole-blood stimulations were performed and cytokine responses measured using Luminex. Gene expression in purified peripheral blood mononuclear cells (PBMCs) was evaluated using an Affymetrix HTA 2.0 gene chip. We found that proportions of CD4+ and CD8+ T cells expressing CD69 increased 24 h after initial panobinostat administration (P < 0.01), followed by an increase in the proportions of CD38+ HLA-DR+-coexpressing CD4+ T cells on day 4 (P = 0.02). Concurrently, proportions of Tregs increased by 40% (P = 0.003). Treg CTLA4 median fluorescent intensity (MFI) increased by 25% (P = 0.007), and CD39 MFI on CD39+ Treg increased by 12% (P = 0.02). Lipopolysaccharide (LPS)-induced inflammatory responses (interleukin-1β [IL-1β], IL-6, IL-12p40, and tumor necrosis factor alpha [TNF...Continue Reading

References

Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Flavio LeoniPaolo Mascagni
Jul 18, 2002·Nature Reviews. Drug Discovery·Ricky W Johnstone
Jul 4, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hnin Thanda AungTimothy Ravasi
Mar 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nainong LiDefu Zeng
May 2, 2009·Archives of Pharmacal Research·Sang-Bae Han, Jae Kwon Lee
Nov 20, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takako Miki-HosokawaToshinori Nakayama
Jan 27, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aleksander M GrabiecKris A Reedquist
Mar 23, 2010·Cell·Charles A Dinarello
May 5, 2010·Immunology and Cell Biology·Javier Vega-RamosPilar Lauzurica
May 19, 2010·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Tatiana AkimovaWayne W Hancock
Mar 30, 2011·Molecular and Cellular Biology·Edwin F de ZoetenWayne W Hancock
May 11, 2011·Molecular Medicine·Charles A DinarelloPaolo Mascagni
Mar 30, 2012·Genes and Immunity·B N VazquezP Lauzurica
Jun 20, 2012·The Journal of Infectious Diseases·Hongbing YangLucy Dorrell
Feb 2, 2013·Human Vaccines & Immunotherapeutics·Thomas Aagaard RasmussenMartin Tolstrup
Dec 21, 2013·Nature·Gilad DoitshWarner C Greene
Jan 3, 2014·The Journal of Clinical Investigation·Alison C West, Ricky W Johnstone
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Sep 18, 2015·PLoS Pathogens·Ole S SøgaardMartin Tolstrup
Dec 23, 2015·Trends in Microbiology·Thomas Aagaard RasmussenOle Schmeltz Søgaard
Nov 12, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tianyu HeCristian Apetrei

❮ Previous
Next ❯

Citations

Jul 18, 2020·Current Opinion in HIV and AIDS·Jesper Damsgaard GunstOle Schmeltz Søgaard
Sep 10, 2019·Frontiers in Microbiology·Paul W DentonMartin Tolstrup
Jan 29, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Renée M Van der SluisSharon R Lewin
Jul 11, 2018·Frontiers in Immunology·Genevieve Tyndale Clutton, R Brad Jones
Feb 26, 2021·JCI Insight·Wouter A van der HeijdenQuirijn de Mast

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme-linked immunosorbent spot
histone acetylation
nuclear translocation
dissection
flow cytometry

Clinical Trials Mentioned

NCT01680094

Software Mentioned

GraphPad Prism
panobinostat
R
LIMMA
FlowJo
Ingenuity pathway analysis ( IPA

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.

© 2022 Meta ULC. All rights reserved