Chemical and genetic control of IFNγ-induced MHCII expression

EMBO Reports
Ruud H WijdevenJacques Neefjes

Abstract

The cytokine interferon-γ (IFNγ) can induce expression of MHC class II (MHCII) on many different cell types, leading to antigen presentation to CD4+ T cells and immune activation. This has also been linked to anti-tumour immunity and graft-versus-host disease. The extent of MHCII upregulation by IFNγ is cell type-dependent and under extensive control of epigenetic regulators and signalling pathways. Here, we identify novel genetic and chemical factors that control this form of MHCII expression. Loss of the oxidative stress sensor Keap1, autophagy adaptor p62/SQSTM1, ubiquitin E3-ligase Cullin-3 and chromatin remodeller BPTF impair IFNγ-mediated MHCII expression. A similar phenotype is observed for arsenite, an oxidative stressor. Effects of the latter can be reversed by the inhibition of HDAC1/2, linking oxidative stress conditions to epigenetic control of MHCII expression. Furthermore, dimethyl fumarate, an antioxidant used for the treatment of several autoimmune diseases, impairs the IFNγ response by manipulating transcriptional control of MHCII We describe novel pathways and drugs related to oxidative conditions in cells impacting on IFNγ-mediated MHCII expression, which provide a molecular basis for the understanding of MHC...Continue Reading

References

Jan 1, 1991·Virchows Archiv. B, Cell Pathology Including Molecular Pathology·H KammaT Iijima
Aug 1, 1991·Toxicology and Applied Pharmacology·E E SikorskiA E Munson
Feb 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A C MorrisJ M Boss
Feb 17, 2001·The Journal of Investigative Dermatology·K Zhu, U Mrowietz
Jun 29, 2001·Nature Immunology·G W Beresford, J M Boss
Sep 12, 2001·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·J M WroblewskiJ R Yannelli
Mar 12, 2002·The Journal of Investigative Dermatology·R LoeweP Petzelbauer
May 6, 2003·European Journal of Immunology·Raffaella MeazzaRoberto S Accolla
Oct 4, 2003·Journal of Leukocyte Biology·Kate SchroderDavid A Hume
May 3, 2005·Nature Reviews. Immunology·Leonidas C Platanias
Oct 4, 2005·Nature Reviews. Immunology·Walter ReithJean-Marc Waldburger
Dec 21, 2005·Brain : a Journal of Neurology·Leonie A BovenJon D Laman
Jun 21, 2007·The Journal of Biological Chemistry·Serhiy PankivTerje Johansen
Nov 6, 2007·Advances in Immunology·Jamie R Schoenborn, Christopher B Wilson
Apr 17, 2008·Environmental Health Perspectives·Angeline S AndrewMargaret R Karagas
Apr 26, 2008·PLoS Genetics·Michelle M A FernandoJohn D Rioux
Sep 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ilona KryczekWeiping Zou
Jul 21, 2009·Cell·Mathew E SowaJ Wade Harper
Oct 13, 2009·Molecular Cell·Dung-Fang LeeMien-Chie Hung
Oct 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·UNKNOWN International MHC and Autoimmunity Genetics NetworkStephen L Hauser
Jun 24, 2010·The EMBO Journal·Roel H WiltingJan-Hermen Dannenberg
Oct 26, 2010·Current Opinion in Immunology·Nancy M ChoiJeremy M Boss
Jan 22, 2011·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Keiko TaguchiMasayuki Yamamoto
Oct 12, 2011·The Journal of Experimental Medicine·Kamran GhoreschiMartin Röcken

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

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.

Related Papers

Current Opinion in Immunology
Tineke van den HoornJacques Neefjes
Journal of Immunology Research
Sujuan DingJun Fang
[Rinshō ketsueki] The Japanese journal of clinical hematology
Motoko Koyama
© 2022 Meta ULC. All rights reserved