Cold exposure protects from neuroinflammation through immunologic reprogramming

ABSTRACT: Summary Autoimmunity is energetically costly, but the impact of a metabolically active state on immunity and immune-mediated diseases is unclear. Ly6Chi 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 Highlights • Cold temperature modulates immunologic and metabolic phenotype of monocytes• Cold promotes energetic trade-off between metabolic adaptations and autoimmunity in mice• Cold exposure lowers MHCII on monocytes and ameliorates neuroinflammation• Reduced T cell priming by monocytes is critical for the cold-induced EAE attenuation Spiljar et al. show that colder temperatures provoke an energetic trade-off between autoimmunity and thermogenesis in mice. Cold decreases MHCII on monocytes at steady state and in various inflammatory conditions including in a mouse model of multiple sclerosis. Further, cold suppresses autoreactive T cell priming and pathogenicity through the modulation of monocytes, thereby ameliorating neuroinflammation.

SUBMITTER: Spiljar M 

PROVIDER: S-EPMC8570411 | biostudies-literature |

REPOSITORIES: biostudies-literature