Jagged-1 is required for the expansion of CD4+ CD25+ FoxP3+ regulatory T cells and tolerogenic dendritic cells by murine mesenchymal stromal cells

• DOI: 10.1186/s13287-015-0021-5
• Publication Date: 2015-03-10T17:54:09Z
• Authors: Emer F Cahill; Laura M Tobin; Fiona Carty; Bernard P Mahon; Karen English
• Keywords: Regulatory T cell

Abstract Introduction Mesenchymal stromal cells (MSC) have well defined immunomodulatory properties including the suppression of lymphocyte proliferation and inhibition dendritic cell (DC) maturation involving both contact soluble factors. These made MSC attractive candidates for cellular therapy. However, mechanism underlying these characteristics remains unclear. This study sought to investigate mechanisms by which induce a regulatory environment. Method Allogeneic bone marrow mesenchymal were cultured with T or in presence absence gamma secretase inhibitor block Notch receptor signalling. examined flow cytometry changes phenotype marker expression. Stable knock down generated examine influence Jagged 1 signalling MSC. Both wildtype knockdown subsequently used vivo an animal model allergic airway inflammation. Results The ligand Jagged-1 was demonstrated be involved expansion (Treg). Additionally, MSC-induced functional semi-mature DC phenotype, further required Treg. MSC, but not reduced pathology mouse Protection mediated associated enhanced Treg lung significantly increased production interleukin (IL)-10 splenocytes re-stimulated allergen. Significantly less IL-10 observed mice treated Conclusions current suggests that MSC-mediated immune modulation involves education dependent manner provides first report importance protection against inflammation .