Expression of toll‐like receptors and their regulatory roles in murine cardiac telocytes

Abstract

Telocytes, newly discovered in the last decade, are interstitial cells found in numerous organs, with multiple proposed potential biological functions. Toll‐like receptors (TLRs) play an important role in innate and adaptive immunity by recognizing pathogen‐associated molecular patterns (PAMPs). However, it is still unknown whether telocytes express these innate receptors. We sought to determine the expression and role of TLRs in telocytes. In our study, we primarily detected TLR1‐9 expression in telocytes. The proliferation, apoptosis and immunoregulatory activity of telocytes activated with or without TLR ligands were determined. Our results showed that purified telocytes expressed TLR2, TLR3 and TLR5. In particular, telocytes expressed high levels of TLR2 as observed using flow cytometry. When we stimulated telocytes with TLR2 or TLR3 agonists (Pam3CSK4, PolyI:C), iNOS expression was greatly increased after Pam3CSK4 treatment. Additionally, telocyte proliferation was reduced and cell apoptosis was increased after TLR agonist stimulation. A co‐culture experiment showed that supernatant from telocytes pretreated with Pam3CSK4 inhibited T cell activation much more than that from untreated telocytes and this effect was mediated by iNOS. Overall, our results demonstrated TLR expression on telocytes for the first time and provided evidence of an immunoregulatory role of telocytes, indicating their clinical potential.

Spatial relationship between telocytes, interstitial cells of Cajal and the enteric nervous system in the human ileum and colon

“…The TCs have an important role in the organization and control of the extracellular matrix, structural support, intercellular communication and creation of the environment . Furthermore, TCs contribute to the regulation of the Wnt pathway in regeneration and through toll‐like receptors in immunoregulation . Accordingly, patients with Crohn's disease and ulcerative colitis showed a reduced amount of TCs in affected bowel segments, as well as reduced amounts of ICCs .…”

“…21 Furthermore, TCs contribute to the regulation of the Wnt pathway in regeneration and through tolllike receptors in immunoregulation. 19,30 Accordingly, patients with ICCs. 24,26 Although the loss of TC and ICC was parallel in inflammatory bowel diseases, 24,26 findings in diabetes mellitus showed that FLC, proven to be identical to TC, 23 were more resistant to degeneration than ICC.…”

Telocytes inhibited inflammatory factor expression and enhanced cell migration in LPS-induced skin wound healing models in vitro and in vivo

“…However, there are much more questions refer to the mechanisms involved in TCs protection function derived from our current study: (1) the exact factors released by TCs or contained in exosomes produced by TCs; (2) the processes that TCs injection and interact with other type of cells such as epithelial cell during inflammation, whether TCs could lead to or reversing epithelial-mesenchymal transition (EMT) et al, (3) were there some other cell types, like immune cells are the target cells of the cell-cell communication of TCs, and whether the recently identified Toll-like receptors (TLR) 4 and 5/ iNOS signaling pathway were involved in this processing [31]? Therefore, the potential bio-functions of TCs in certain pathological conditions in wounds healing and mechanisms of cell-cell communication between TCs and other cells need to be further explored.…”

Morpho-functional changes of cardiac telocytes in isolated atrial amyloidosis in patients with atrial fibrillation

“…TCs act as immunoregulators expressing toll-like receptors TLR 2, TLR 3, TLR 5 65 . Transfer of TCs exosomes into infarct-affected rat myocardium attenuates cardiac fibrosis, improves cardiac function, and increases angiogenesis 36 .…”