Abstract
Notch signaling coordinates numerous cellular processes and has been implicated in many pathological conditions, including rheumatoid arthritis (RA). Although the role of Notch signaling in development, maturation, differentiation, and activation of lymphocytes has been comprehensively reported, less is known about its role in myeloid cells. Certainly, limited data are available about the role of Notch signaling in macrophages during inflammation and infection. In this review, we discuss the recent advances pertaining to the role of Notch signaling in differentiation, activation, and metabolism of macrophages during inflammation and infection. We also highlight the reciprocal interplay between Notch signaling and other signaling pathways in macrophages under different inflammatory and infectious conditions including pathogenesis of RA. Finally, we discuss approaches that could consider Notch signaling as a potential therapeutic target against infection- and inflammation-driven diseases.
Highlights
Notch Signaling and Its Core ComponentsNotch signaling is a juxtacrine signaling that mediates cell-to-cell communication through the receptor–ligand interaction between neighboring cells [1]
This study reported a positive correlation between M1/M2 ratio and Notch signaling in the mucosa of chronic Crohn’s disease (CD) patients [63]
Notch signaling is essential in all cellular processes, and its dysregulation has been linked to many pathological disorders including rheumatoid arthritis (RA)
Summary
Notch signaling is a juxtacrine signaling that mediates cell-to-cell communication through the receptor–ligand interaction between neighboring cells [1]. It is a highly conserved regulatory pathway that is found in all multicellular organisms from Drosophila to mammals [1,2]. NICD has a transcriptional activity and contains several functional elements including a PEST (proline/glutamic acid/serine/threonine) domain, ankyrin domains, recombinant recognition sequence binding protein at the J Kappa site (RBP-J)-association module (RAM) domain, and nuclear localization signals [3,4]
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