Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M

M. Elizabeth Deerhake, Keiko Danzaki, Makoto Inoue, Emre D. Cardakli, Toshiaki Nonaka, Nupur Aggarwal, William E. Barclay, Ru Rong Ji, Mari L. Shinohara

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)484-498.e8
JournalImmunity
Volume54
Issue number3
DOIs
StatePublished - Mar 9 2021

Keywords

  • astrocytes
  • C-type lectin receptors
  • Card9
  • CLRs
  • Dectin-1/Clec7a
  • Gal-9
  • Galectin-9
  • innate immunity
  • MS
  • multiple sclerosis
  • neuroimmunology
  • Oncostatin M
  • Osm
  • OSMR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M'. Together they form a unique fingerprint.

Cite this