Liver inflammation abrogates immunological tolerance induced by Kupffer cells (original) (raw)

2015, Hepatology (Baltimore, Md.)

The liver is essential for inducing immunological tolerance towards harmless antigens to maintain immune system homeostasis. However, the precise cellular mechanisms of tolerance induction against particle-bound antigens, the role of the local hepatic microenvironment and implications for therapeutic targets in immune-mediated diseases are currently unclear. In order to elucidate cellular mechanisms of tolerance induction in healthy and injured liver, we developed a novel in vivo system combining the systemic delivery of low-dose peptide antigens coupled to inert particles, immunological read-outs and sophisticated intravital multiphoton microscopy based imaging of the liver in mice. We show that liver resident macrophages, Kupffer cells (KC), but not hepatic monocyte-derived macrophages or dendritic cells (DC), are the central cellular scavenger for circulating particle-associated antigens in homeostasis. KC-associated antigen presentation induces CD4 T cell arrest, expansion of na...

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