Dectin-1 limits central nervous system autoimmunity through a non-canonical pathway
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (preLights)
Abstract
Pathologic roles for innate immunity in neurologic disorders are well-described, but protective aspects of the immune response are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. However, we found that Dectin-1 is protective in experimental autoimmune encephalomyelitis (EAE), while its canonical signaling mediator, Card9, promotes the disease. Notably, Dectin-1 does not respond to heat-killed Mycobacteria , an adjuvant to induce EAE. Myeloid cells mediate the protective function of Dectin-1 in EAE and upregulate gene expression of neuroprotective molecules, including Oncostatin M (Osm) through a non-canonical Card9-independent pathway, mediated by NFAT. Furthermore, we found that the Osm receptor (OsmR) functions specifically in astrocytes to reduce EAE severity. Our study revealed a new mechanism of protective myeloid-astrocyte crosstalk regulated by a non-canonical Dectin-1 pathway and identifies novel therapeutic targets for CNS autoimmunity.
Graphical Abstract
-
Dectin-1 is a protective C-type lectin receptor (CLR) in experimental autoimmune encephalomyelitis (EAE)
-
Dectin-1 promotes expression of Osm , a neuroprotective IL-6 family cytokine, in myeloid cells
-
OsmR signaling in astrocytes limits EAE progression and promotes remission
-
Non-canonical Card9-independent signaling drives a distinct Dectin-1-mediated transcriptional program to induce expression of Osm and other factors with protective or anti-inflammatory functions
Article activity feed
-
Excerpt
Dectin-1 mediates the induction of an unexpected anti-inflammatory program in myeloid cells and limits neuroinflammation
-
