Toll-like receptor (TLR)7 and TLR9 agonists enhance interferon (IFN) beta-1a's immunoregulatory effects on B cells in patients with relapsing-remitting multiple sclerosis (RRMS).
We report that B cells from patients with RRMS have decreased endogenous IFN-β secretion and deficient IFN receptor (IFNAR)1/2 and TLR7 gene expression in comparison to healthy controls (HCs), which may contribute to disregulation of cytokine secretion by B cells. We propose that TLR7 and TLR9 stimulation with loxorubin (LOX) and CpG, in combination with exogenous IFN-β may effectively reconstitute endogenous IFN-β production deficit and induce the secretion of immunoregulatory cytokines by B cells. Both LOX/IFN-β and CpG/IFN-β in-vitro treatments of B cells from RRMS patients induced higher endogenous IFN-β gene expression in comparison to the exogenous IFN-β alone. CpG/IFN-β combination induced higher secretion of IL-10, TGF-β, and IL-27 in comparison to stimulation with IFN-β. Our study provides a basis for future clinical studies employing IFN-β and TLR7/9 agonists, which may enhance the resolution of the inflammatory response in RRMS.
Duke Scholars
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- Toll-Like Receptor 9
- Toll-Like Receptor 7
- Tetraspanin 29
- STAT1 Transcription Factor
- Neurology & Neurosurgery
- Myeloid Differentiation Factor 88
- Multiple Sclerosis, Relapsing-Remitting
- Methylprednisolone
- Male
- Interferon-beta
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Toll-Like Receptor 9
- Toll-Like Receptor 7
- Tetraspanin 29
- STAT1 Transcription Factor
- Neurology & Neurosurgery
- Myeloid Differentiation Factor 88
- Multiple Sclerosis, Relapsing-Remitting
- Methylprednisolone
- Male
- Interferon-beta