| First Author | White MPJ | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 259 |
| PubMed ID | 29321652 | Mgi Jnum | J:260226 |
| Mgi Id | MGI:6148512 | Doi | 10.1038/s41598-017-18543-z |
| Citation | White MPJ, et al. (2018) Innate IFN-gamma ameliorates experimental autoimmune encephalomyelitis and promotes myeloid expansion and PDL-1 expression. Sci Rep 8(1):259 |
| abstractText | The innate immune system plays a central role in the immune-mediated pathology of multiple sclerosis, and is a therapeutic target for progressive disease. Recently, it has been demonstrated that MIS416, a novel immunomodulatory microparticle that activates NOD-2 and TLR-9-signaling, has disease-modifying activity in multiple sclerosis models. This activity is dependent on innate IFN-gamma; however, the precise immune regulatory mechanisms amplified by MIS416 have not previously been determined. Using the experimental autoimmune encephalomyelitis model, MIS416 treatment was associated with IFN-gamma-dependant expansion of Treg number and increased suppressive function; however, these cells did not account for disease reduction. Additionally, MIS416 treatment stimulated increased nitric oxide production that was IFN-gamma-dependant but dispensable for protection. Finally, MIS416-mediated protection was shown to correlate with IFN-gamma-dependant expansion of PDL-1-expressing peripheral myeloid cells, a subset of which was found to be selectively recruited to the brain. This central nervous system trafficking was independent of neuro-inflammatory signals as it occurred in MIS416-treated healthy mice. Together, these findings provide insight into regulatory myeloid cell activities amplified by MIS416-mediated NOD-2 and TLR-9 signalling and highlight the potential importance of these cells in accessing the brain where they may act locally and contribute to the control of neuroinflammation. |
