Synergistic Targeting of Innate Receptors TLR7 and NOD2 for Therapeutic Intervention in Multiple Sclerosis

Magdalena Dubik, Joanna Marczynska-Grzelak, Michael Zaucha Sørensen, Ruthe Storgaard Dieu, Dominika Rusin, Eydís Sigurdardóttir Schiöth, Bita Ramazani, Rouhin Belal, Bhavya Ojha, Jonathan Krieger, Dina S. Arengoth, Agnieszka Wlodarczyk, Trevor Owens, Reza Khorooshi*

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

12 Downloads (Pure)

Abstract

Regulation of neuroinflammation is critical for maintaining central nervous system (CNS) homeostasis and holds therapeutic promise in autoimmune diseases such as multiple sclerosis (MS). Previous studies have highlighted the significance of selective innate signaling in triggering anti-inflammatory mechanisms, which play a protective role in an MS-like disease, experimental autoimmune encephalomyelitis (EAE). However, the individual intra-CNS administration of specific innate receptor ligands or agonists, such as for toll-like receptor 7 (TLR7) and nucleotide-binding oligomerization-domain-containing protein 2 (NOD2), failed to elicit the desired anti-inflammatory response in EAE. In this study, we investigated the potential synergistic effect of targeting both TLR7 and NOD2 simultaneously to prevent EAE progression. Our findings demonstrate that simultaneous intrathecal administration of NOD2- and TLR7-agonists led to synergistic induction of Type I IFN (IFN I) and effectively suppressed EAE in an IFN I-dependent manner. Suppression of EAE was correlated with a significant decrease in the infiltration of monocytes, granulocytes, and natural killer cells, reduced demyelination, and downregulation of IL-1β, CCL2, and IFNγ gene expression in the spinal cord. These results underscore the therapeutic promise of concurrently targeting the TLR7 and NOD2 pathways in alleviating neuroinflammation associated with MS, paving the way for novel and more efficacious treatment strategies.

OriginalsprogEngelsk
Artikelnummer7462
TidsskriftInternational Journal of Molecular Sciences
Vol/bind25
Udgave nummer13
Antal sider10
ISSN1661-6596
DOI
StatusUdgivet - jul. 2024

Fingeraftryk

Dyk ned i forskningsemnerne om 'Synergistic Targeting of Innate Receptors TLR7 and NOD2 for Therapeutic Intervention in Multiple Sclerosis'. Sammen danner de et unikt fingeraftryk.

Citationsformater