HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Cells resident to precision templated 40-µm pore scaffolds generate small extracellular vesicles that affect CD4+ T cell phenotypes through regulatory TLR4 signaling.

Abstract
Precision porous templated scaffolds (PTS) are a hydrogel construct of uniformly sized interconnected spherical pores that induce a pro-healing response (reducing the foreign body reaction, FBR) exclusively when the pores are 30-40µm in diameter. Our previous work demonstrated the necessity of Tregs in the maintenance of PTS pore size specific differences in CD4+ T cell phenotype. Work here characterizes the role of Tregs in the responses to implanted 40µm and 100µm PTS using WT and FoxP3+ cell (Treg) depleted mice. Proteomic analyses indicate that integrin signaling, monocytes/macrophages, cytoskeletal remodeling, inflammatory cues, and vesicule endocytosis may participate in Treg activation and the CD4+ T cell equilibrium modulated by PTS resident cell-derived small extracellular vesicles (sEVs). The role of MyD88-dependent and MyD88-independent TLR4 activation in PTS cell-derived sEV-to-T cell signaling is quantified by treating WT, TLR4ko, and MyD88ko splenic T cells with PTS cell-derived sEVs. STAT3 and mTOR are identified as mechanisms for further study for pore-size dependent PTS cell-derived sEV-to-T cell signaling. STATEMENT OF SIGNIFICANCE: Unique cell populations colonizing only within 40µm pore size PTS generate sEVs that resolve inflammation by modifying CD4+ T cell phenotypes through TLR4 signaling.
AuthorsT F Hady, B Hwang, R L Waworuntu, B D Ratner, J D Bryers
JournalActa biomaterialia (Acta Biomater) Vol. 166 Pg. 119-132 (08 2023) ISSN: 1878-7568 [Electronic] England
PMID37150279 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • Toll-Like Receptor 4
  • Myeloid Differentiation Factor 88
Topics
  • Mice
  • Animals
  • Toll-Like Receptor 4 (metabolism)
  • Myeloid Differentiation Factor 88 (metabolism)
  • Proteomics
  • Signal Transduction
  • CD4-Positive T-Lymphocytes
  • Extracellular Vesicles (metabolism)
  • Phenotype

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: