The proteoglycan biglycan enhances antigen‐specific T cell activation potentially via MyD88 and TRIF pathways and triggers autoimmune perimyocarditis

Abstract

Biglycan is a proteoglycan present in extracellular matrix of a variety of organs and has been reported to be overexpressed in myocardial infarction. Myocardial infarction may be complicated by perimyocarditis through to date unclear mechanisms. Our aim was to investigate the capacity of TLR2/TLR4 ligand biglycan to enhance the presentation of specific cardiac Ags. In vitro, Ovapulsed DCs from WT, TLR2, TLR4, MyD88 or TRIF deficient mice were treated with LPS or biglycan and incubated with Ovarecognizing MHCI‐ or MHCII‐restricted T cells. Biglycan enhanced cross‐priming of MHCI‐restricted T cells in both TLR2‐ and TLR4‐ pathway dependent manner. Ova‐specific activation of MHCII‐restricted T cells was TLR4‐dependent. Our in vivo correlate was a model of autoimmune perimyocarditis triggered by injection of cardiac‐Ag pulsed DCs. Biglycan‐treated DCs triggered perimyocarditis in an intensity comparable to LPS‐treated DCs. Substitution with TLR4‐deficient DCs abolished this effect. In a second approach, WT and biglycan‐deficient mice were followed two weeks after induction of myocardial infarction. WT mice showed significantly higher T‐lymphocyte infiltration than biglycan‐deficient mice. We conclude that biglycan may enhance Ag‐specific T cell priming via MyD88 and TRIF and stimulate autoimmune perimyocarditis.