Cold exposure protects from neuroinflammation through immunologic reprogramming

Martina Spiljar; Karin Steinbach; Dorothée Rigo; Nicolas Suárez-Zamorano; Ingrid Wagner; Noushin Hadadi; Ilena Vincenti; Nicolas Page; Bogna Klimek; Mary-Aude Rochat; Mario Kreutzfeldt; Claire Chevalier; Ozren Stojanović; Olivia Bejuy; Didier Colin; Matthias Mack; Dilay Cansever; Melanie Greter; Doron Merkler; Mirko Trajkovski

doi:10.1016/j.cmet.2021.10.002

Cold exposure protects from neuroinflammation through immunologic reprogramming

Cell Metab. 2021 Nov 2;33(11):2231-2246.e8. doi: 10.1016/j.cmet.2021.10.002. Epub 2021 Oct 22.

Authors

Martina Spiljar¹, Karin Steinbach², Dorothée Rigo¹, Nicolas Suárez-Zamorano¹, Ingrid Wagner², Noushin Hadadi¹, Ilena Vincenti², Nicolas Page², Bogna Klimek², Mary-Aude Rochat¹, Mario Kreutzfeldt², Claire Chevalier¹, Ozren Stojanović¹, Olivia Bejuy³, Didier Colin⁴, Matthias Mack⁵, Dilay Cansever⁶, Melanie Greter⁶, Doron Merkler⁷, Mirko Trajkovski⁸

Affiliations

¹ Department of Cell Physiology and Metabolism, Faculty of Medicine, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
² Department of Pathology and Immunology, Faculty of Medicine, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland.
³ CIBM Centre for BioMedical Imaging, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
⁴ Small Animal Preclinical Imaging Platform, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
⁵ Department of Internal Medicine II - Nephrology, University Hospital Regensburg, Regensburg, Germany.
⁶ Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
⁷ Department of Pathology and Immunology, Faculty of Medicine, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland. Electronic address: doron.merkler@unige.ch.
⁸ Department of Cell Physiology and Metabolism, Faculty of Medicine, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: mirko.trajkovski@unige.ch.

Abstract

Autoimmunity is energetically costly, but the impact of a metabolically active state on immunity and immune-mediated diseases is unclear. Ly6C^hi monocytes are key effectors in CNS autoimmunity with an elusive role in priming naive autoreactive T cells. Here, we provide unbiased analysis of the immune changes in various compartments during cold exposure and show that this energetically costly stimulus markedly ameliorates active experimental autoimmune encephalomyelitis (EAE). Cold exposure decreases MHCII on monocytes at steady state and in various inflammatory mouse models and suppresses T cell priming and pathogenicity through the modulation of monocytes. Genetic or antibody-mediated monocyte depletion or adoptive transfer of Th1- or Th17-polarized cells for EAE abolishes the cold-induced effects on T cells or EAE, respectively. These findings provide a mechanistic link between environmental temperature and neuroinflammation and suggest competition between cold-induced metabolic adaptations and autoimmunity as energetic trade-off beneficial for the immune-mediated diseases.

Keywords: T cell priming; autoimmunity; bone marrow; cold exposure; experimental autoimmune encephalomyelitis; immunometabolism; inflammation; monocytes; multiple sclerosis; neuroinflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adoptive Transfer
Animals
Autoimmunity
Encephalomyelitis, Autoimmune, Experimental*
Mice
Mice, Inbred C57BL
Neuroinflammatory Diseases*
Th17 Cells