Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M.
| Publication Type | Academic Article |
| Authors | Deerhake M, Danzaki K, Inoue M, Cardakli E, Nonaka T, Aggarwal N, Barclay W, Ji R, Shinohara M |
| Journal | Immunity |
| Volume | 54 |
| Issue | 3 |
| Pagination | 484-498.e8 |
| Date Published | 02/12/2021 |
| ISSN | 1097-4180 |
| Keywords | Astrocytes, Brain, CARD Signaling Adaptor Proteins, Encephalomyelitis, Autoimmune, Experimental, Lectins, C-Type, Multiple Sclerosis, Myeloid Cells, Neurogenic Inflammation, Receptors, Mitogen |
| 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. |
| DOI | 10.1016/j.immuni.2021.01.004 |
| PubMed ID | 33581044 |
| PubMed Central ID | PMC7956124 |