Immunity. 2021 Feb 8;S1074-7613(21)00027-3. doi: 10.1016/j.immuni.2021.01.004. | PubMed

M Elizabeth Deerhake¹, Keiko Danzaki¹, Makoto Inoue², Emre D Cardakli¹, Toshiaki Nonaka¹, Nupur Aggarwal¹, William E Barclay¹, Ru-Rong Ji³, Mari L Shinohara⁴

1. Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
2. Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.
3. Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA.
4. Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: mari.shinohara@duke.edu.

Abstract

Pathologic roles of innate immunity in neurologic disorders are well described, but their beneficial aspects are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. Here, we report that Dectin-1 limited experimental autoimmune encephalomyelitis (EAE), while its downstream signaling molecule, Card9, promoted the disease. Myeloid cells mediated the pro-resolution function of Dectin-1 in EAE with enhanced gene expression of the neuroprotective molecule, Oncostatin M (Osm), through a Card9-independent pathway, mediated by the transcription factor NFAT. Furthermore, we find that the Osm receptor (OsmR) functioned specifically in astrocytes to reduce EAE severity. Notably, Dectin-1 did not respond to heat-killed Mycobacteria, an adjuvant to induce EAE. Instead, endogenous Dectin-1 ligands, including galectin-9, in the central nervous system (CNS) were involved to limit EAE. Our study reveals a mechanism of beneficial myeloid cell-astrocyte crosstalk regulated by a Dectin-1 pathway and identifies potential therapeutic targets for autoimmune neuroinflammation.

Presented By M Elizabeth Deerhake | ORCID iD