Paracrine regulations of IFN-γ secreting CD4+ T cells by lumican and biglycan are protective in allergic contact dermatitis

Abstract

The extracellular matrix (ECM) is known to regulate innate immune cells but its role in T cell functions is poorly understood. Here, we show a protective role for ECM proteoglycans, lumican and biglycan in hapten-induced contact dermatitis that is achieved through limiting proinflammatory CD4+T cells. Lumican and biglycan-null mice develop significant inflammation with greater numbers of CD4+T cells in hapten-challenged ear pinnae, while their draining lymph nodes show increased T-bet-STAT1 signaling, Th1 commitment, and IFN-{gamma} secreting CD4+T cell proliferation. Wild type mouse lymph node fibroblastic reticular cells secrete lumican, biglycan and decorin, a related proteoglycan, while none are expressed by naive or activated T cells. In vitro, lumican and biglycan co-localize with LFA-1 on T cell surfaces, and all three proteoglycans suppress LFA-1 mediated T cell activation. Overall, this study elucidates a novel paracrine regulation of Th1 cells by ECM proteoglycans to limit inflammation and tissue damage.