In Vivo Interleukin-13-Primed Macrophages Contribute to Reduced Alloantigen-Specific T Cell Activation and Prolong Immunological Survival of Allogeneic Mesenchymal Stem Cell Implants (pages 1971–1984)
Chloé J. Hoornaert, Evi Luyckx, Kristien Reekmans, Maxime Dhainaut, Caroline Guglielmetti, Debbie Le Blon, Dearbhaile Dooley, Erik Fransen, Jasmijn Daans, Louca Verbeeck, Alessandra Quarta, Nathalie De Vocht, Evi Lemmens, Herman Goossens, Annemie Van der Linden, Valerie D. Roobrouck, Catherine Verfaillie, Sven Hendrix, Muriel Moser, Zwi N. Berneman and Peter Ponsaerts
Version of Record online: 28 MAR 2016 | DOI: 10.1002/stem.2360
Upon transplantation of IL13-engineered MSCs into allogeneic mice, local IL13 production modulated both innate and adaptive immune responses, ultimately resulting in prolonged MSC allograft survival. (A): FVB mouse-derived MSC-Luc/eGFP and MSC-Luc/eGFP/IL13 implants in the muscle or brain of C57BL/6 mice. Expression of Arg1, a marker of alternative M2a activation, was restricted to F4/80+ macrophages infiltrating IL13-producing MSC grafts. (B): T cells from naive, FVB MSC-transplanted or FVB MSC-IL13-transplanted C57BL/6 mice were analyzed by flow cytometry, with or without prior FVB MSC stimulation. IL13-expressing MSC allografts induced significantly fewer alloreactive CD8+ T cells than wildtype MSC allografts. *p<0.05; ***p<0.001 (C+D): Quantitative analysis of in vivo bioluminescence imaging of intramuscular (panel C) and intracerebral (panel D) FVB MSC-Luc/eGFP or FVB MSC-Luc/eGFP/IL13 allografts in C57BL/6 mice. Background radiance is demarcated by the gray area. IL13-expressing MSC allografts display a prolonged survival in both muscle and brain tissue of immune competent mice. **p<0.01 Abbreviations: MSC, mesenchymal stem cell; IL13, interleukin-13; Luc, firefly luciferase; eGFP, enhanced green fluorescent protein; Arg1, arginase-1.