Abstract
Dental mesenchymal stromal cells (MSCs) are a promising tool for clinical application in and beyond dentistry. These cells possess multilineage differentiation potential and immunomodulatory properties. Due to their localization in the oral cavity, these cells could sometimes be exposed to different bacteria and viruses. Dental MSCs express various Toll-like receptors (TLRs), and therefore, they can recognize different microorganisms. The engagement of TLRs in dental MSCs by various ligands might change their properties and function. The differentiation capacity of dental MSCs might be either inhibited or enhanced by TLRs ligands depending on their nature and concentrations. Activation of TLR signaling in dental MSCs induces the production of proinflammatory mediators. Additionally, TLR ligands alter the immunomodulatory ability of dental MSCs, but this aspect is still poorly explored. Understanding the role of TLR signaling in dental MSCs physiology is essential to assess their role in oral homeostasis, inflammatory diseases, and tissue regeneration.
Highlights
Specialty section: This article was submitted to Oral Infections and Microbes, a section of the journal Frontiers in Oral Health
The International Society for Cell and Gene Therapy (ISCT) defines mesenchymal stromal cells (MSCs) as plastic-adherent fibroblast-like cells; expressing mesenchymal surface markers CD73, CD90, and CD105; lacking hematopoietic surface markers CD11b, CD14, CD34, CD45, and HLA-DR; and possessing the ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro [13, 14]
The immunomodulatory capacity of dental MSCs is usually low and is boosted by different inflammatory cytokines like IFNγ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. These cytokines are produced by the activated immune cells and upregulate the expression of different immunomodulatory factors in dental MSCs, e.g., indolamine-2,3-dioxygenase 1 (IDO-1), prostaglandin E2 (PGE2), TNF-α-stimulated gene 6 (TSG-6), programmed cell death-ligand 1 (PD-L1), and PD-L2 [36,37,38,39,40]
Summary
Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria. Dental mesenchymal stromal cells (MSCs) are a promising tool for clinical application in and beyond dentistry These cells possess multilineage differentiation potential and immunomodulatory properties. Dental MSCs express various Toll-like receptors (TLRs), and they can recognize different microorganisms. The engagement of TLRs in dental MSCs by various ligands might change their properties and function. Activation of TLR signaling in dental MSCs induces the production of proinflammatory mediators. TLRs are type I transmembrane proteins consisting of extracellular leucine-rich repeats (LRR) and intracellular toll/interleukin (IL)-1 receptor domains. Various human TLRs differ in the number of LRR and domain structures, leading to recognizing different ligands [5]. TLRs and Dental MSCs endogenous ligands released from damaged tissue or dead cells [11]. Ligand binding to TLR-3 activates the TRIF-dependent pathway and induces type I interferon (IFN) signaling. TLR-4 activates both NFκB mediated by MyD88 and type I IFN pathway through TRAM/TRIF [3]
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