Cold exposure protects from neuroinflammation through immunologic reprogramming

doi:10.1016/j.cmet.2021.10.002

Cell Metabolism

Volume 33, Issue 11, 2 November 2021, Pages 2231-2246.e8

https://doi.org/10.1016/j.cmet.2021.10.002 Get rights and content

Under a Creative Commons license

open access

Highlights

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Cold temperature modulates immunologic and metabolic phenotype of monocytes
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Cold promotes energetic trade-off between metabolic adaptations and autoimmunity in mice
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Cold exposure lowers MHCII on monocytes and ameliorates neuroinflammation
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Reduced T cell priming by monocytes is critical for the cold-induced EAE attenuation

Summary

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.

Graphical abstract

Keywords

monocytes

experimental autoimmune encephalomyelitis

immunometabolism

cold exposure

multiple sclerosis

bone marrow

neuroinflammation

autoimmunity

T cell priming

inflammation

Data and Code Availability

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All sequencing data generated in this study are deposited at NCBI Gene Expression Omnibus (GEO) repository with accession numbers GSE172021 and GSE183321, and are publicly available as of the date of publications. Microscopy data reported in this paper will be shared by the lead contact upon request.
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The scripts used for the RNaseq data analysis and generating figures are available at https://github.com/Nhadadi/EAE_mouse_RNaseqAnalysis_multiTissue
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Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

⁹: Present address: Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, USA

¹⁰: These authors contributed equally

¹¹: Lead contact