Lamin A/C deficiency in CD4+ T-cells enhances regulatory T-cells and prevents inflammatory bowel disease

The Journal of Pathology
Raquel Toribio-FernándezJose M Gonzalez-Granado

Abstract

The mechanisms by which lamin A/C in CD4+ T-cells control intestinal homeostasis and can cause inflammatory bowel disease (IBD) are unknown. Here, we explore lamin A/C in a mouse model of IBD. Adoptive transfer to Rag1-/- mice of Lmna-/- CD4+ T-cells, which have enhanced regulatory T-cells (Treg) differentiation and function, induced less severe IBD than wild-type T-cells. Lamin A/C deficiency in CD4+ T-cells enhanced transcription of the Treg master regulator FOXP3, thus promoting Treg differentiation, and reduced Th1 polarization, due to epigenetic changes in the Th1 master regulator T-bet. In mesenteric lymph nodes, retinoic acid (RA) released by CD103+ dendritic cells downregulated lamin A/C in CD4+ T-cells, enhancing Treg differentiation. However, non-RA-producing CD103- dendritic cells predominated in peripheral lymph nodes, facilitating lamin A/C expression in CD4+ T-cells and therefore Th1 differentiation. Our findings establish lamin A/C as a key regulator of Th differentiation in physiological conditions and show it as a potential immune-regulatory target in IBD. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

References

Jul 1, 1988·Medical Toxicology and Adverse Drug Experience·M DavidN J Lowe
Mar 1, 2000·Biochemical and Biophysical Research Communications·K OkumuraN Nakajima
Mar 20, 2001·The Journal of Clinical Investigation·M M KosiewiczF Cominelli
Jun 4, 2002·Nature Medicine·Markus F NeurathLaurie H Glimcher
Nov 1, 2002·Nucleic Acids Research·Caroline DreuilletMichèle Ernoult-Lange
Dec 12, 2002·Molecular Biology of the Cell·Ewa MarkiewiczChristopher J Hutchison
Jul 29, 2004·The Journal of Biological Chemistry·Akio MorinobuJohn J O'Shea
Oct 16, 2004·Immunity·Makoto IwataSi-Young Song
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria A Curotto de LafailleJuan J Lafaille
Jul 21, 2006·Nature Immunology·Simon J Davis, P Anton van der Merwe
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Holm H UhligFiona Powrie
Apr 25, 2007·Experimental Cell Research·Eric C Schirmer, Roland Foisner
Jul 11, 2007·The Journal of Experimental Medicine·Cheng-Ming SunYasmine Belkaid
Mar 4, 2008·Nature Cell Biology·Paola Scaffidi, Tom Misteli
Nov 19, 2008·The Journal of Cell Biology·José María GonzálezVicente Andrés
Dec 17, 2008·Annals of the New York Academy of Sciences·Karina Pino-LagosRandolph J Noelle
Jul 7, 2009·Archivum Immunologiae Et Therapiae Experimentalis·Andrzej SzkaradkiewiczBarbara Zwoździak
Dec 30, 2009·The Journal of Cell Biology·Vicente Andrés, José M González
Mar 3, 2010·Annual Review of Immunology·Jinfang ZhuWilliam E Paul
May 22, 2010·Seminars in Immunology·Toshinori Nakayama, Masakatsu Yamashita
Jul 7, 2010·The Journal of Experimental Medicine·Matthias Merkenschlager, Harald von Boehmer
Sep 10, 2010·Cold Spring Harbor Perspectives in Biology·Thomas DechatRobert D Goldman
May 10, 2011·Drug Design, Development and Therapy·John K TriantafillidisFilippos Georgopoulos
Mar 6, 2012·Nature·Tamer T OnderGeorge Q Daley
Apr 5, 2012·Clinical & Developmental Immunology·Rishi Vishal LuckheeramBing Xia
Apr 27, 2012·International Journal of Inflammation·Thomas Lindebo HolmStine Reedtz-Runge
May 9, 2012·Frontiers in Immunology·Angelika SchmidtPeter H Krammer
Jun 19, 2013·Frontiers in Immunology·Chang H Kim

❮ Previous
Next ❯

Citations

Jun 2, 2020·The Journal of Experimental Medicine·Dan WuMegan K Levings
Aug 29, 2020·International Journal of Molecular Sciences·Angela SaezJose M Gonzalez-Granado
Nov 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marika SjöqvistCecilia Sahlgren
Mar 7, 2021·Communications Biology·Andrea NuzzoJames R Brown
Mar 4, 2021·Trends in Immunology·Brandon L Walling, Philip M Murphy
Aug 24, 2021·Frontiers in Cell and Developmental Biology·Julien RecordLisa S Westerberg

❮ Previous
Next ❯

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.