Deletion of the Mineralocorticoid Receptor in Myeloid Cells Attenuates Central Nervous System Autoimmunity

Frontiers in Immunology
Elena Montes-CobosFred Lühder

Abstract

Myeloid cells play an important role in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Monocytes, macrophages, and microglia can adopt two distinct phenotypes, with M1-polarized cells being more related to inflammation and autoimmunity while M2-polarized cells contribute to tissue repair and anti-inflammatory processes. Here, we show that deletion of the mineralocorticoid receptor (MR) in bone marrow-derived macrophages and peritoneal macrophages caused their polarization toward the M2 phenotype with its distinct gene expression, altered phagocytic and migratory properties, and dampened NO production. After induction of EAE, mice that are selectively devoid of the MR in their myeloid cells (MR(lysM) mice) showed diminished clinical symptoms and ameliorated histological hallmarks of neuroinflammation. T cells in peripheral lymphoid organs of these mice produced less pro-inflammatory cytokines while their proliferation and the abundance of regulatory T cells were unaltered. The numbers of inflammatory monocytes and reactive microglia in the central nervous system (CNS) in MR(lysM) mice were significantly lower and they adopted an M2-polarized phenotype based on th...Continue Reading

References

Oct 1, 1990·The Journal of Experimental Medicine·I HuitingaC D Dijkstra
May 1, 1987·Journal of Neurology, Neurosurgery, and Psychiatry·N M MilliganD A Compston
Oct 1, 1996·Immunobiology·W BrückH Lassmann
Jan 23, 1999·Journal of Neuroimmunology·A van der GoesC D Dijkstra
Jan 6, 2000·Transgenic Research·B E ClausenI Förster
Feb 24, 2001·Acta Neuropathologica·S Litchfield, Z Nagy
May 7, 2003·The Journal of Experimental Medicine·Estelle BettelliVijay K Kuchroo
Jun 18, 2003·Trends in Immunology·Vincenzo BrontePaola Zanovello
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paulo C RodriguezAugusto C Ochoa
Jan 25, 2005·Nature Medicine·Frank L HeppnerAdriano Aguzzi
Apr 27, 2005·Brain Research. Brain Research Reviews·Jerome J A HendriksChristine D Dijkstra
Jun 11, 2005·Heart Failure Reviews·John W Funder
Dec 22, 2005·Proceedings of the National Academy of Sciences of the United States of America·Stefan BergerGünther Schütz
Oct 25, 2007·Brain : a Journal of Neurology·Manuel A Friese, Lars Fugger
Jun 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Simone WüstHolger M Reichardt
Jun 18, 2009·Brain : a Journal of Neurology·Alexander MildnerMarco Prinz
Jul 21, 2009·Journal of Molecular Endocrinology·Jun Yang, Morag J Young
Nov 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anneli JägerVijay K Kuchroo
Dec 2, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrés A HerradaAlexis M Kalergis
Aug 11, 2010·The Journal of Clinical Investigation·Michael G UsherRichard M Mortensen
Nov 26, 2010·Stroke; a Journal of Cerebral Circulation·Ryan A FrielerRichard M Mortensen
Mar 9, 2011·American Journal of Physiology. Renal Physiology·Caroline RonzaudStefan Berger
Sep 16, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nils SchweingruberFred Lühder
Nov 2, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anna KleimanJan P Tuckermann
Jan 4, 2012·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Shawn RoseHarris Perlman
Mar 8, 2013·Nature·Markus KleinewietfeldDavid A Hafler
Apr 16, 2013·Trends in Molecular Medicine·Aiden HaghikiaLars Fugger
Oct 18, 2013·Integrated Blood Pressure Control·John W Funder
Mar 14, 2014·Journal of Cardiovascular Pharmacology·Peter KolkhofStefan Schäfer
Jul 9, 2014·The Journal of Experimental Medicine·Ryo YamasakiRichard M Ransohoff

❮ Previous
Next ❯

Citations

May 15, 2018·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Paulo W PiresAnne M Dorrance
Sep 19, 2019·Acta Physiologica·Jonatan Barrera-Chimal, Frederic Jaisser
Apr 11, 2019·Frontiers in Pharmacology·Jiaying WangQiaojun He
Dec 14, 2018·Hypertension·Daniela FraccarolloJohann Bauersachs
Apr 10, 2021·Biochemistry. Biokhimii︠a︡·Alexey P BolshakovNatalia V Gulyaeva
May 28, 2019·Kidney International·Jonatan Barrera-ChimalFrederic Jaisser

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
lavage
FCS
ELISA
Assay
FACS

Software Mentioned

FlowJo
ImageJ

Related Concepts

Related Feeds

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.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here