Dr. Blumberg and his co-investigator, Dr. Lencer, propose to study the expression and possible function of the neonatal Fc receptor for IgG (FcRn) in adult intestinal cells. This receptor, normally expressed at high levels in neonatal epithelia that are responsible for selective uptake and transcellular transport of maternal IgG, has recently been identified in several adult tissues including intestine, liver and endothelium. The adult expression has resulted in a renewed interest in this receptor and has led to speculation over its possible roles in the adult immune system, including its possible involvement in transport of IgG or immune complexes and in IgG turnover. The present proposal focuses on the FcRn in intestinal epithelial cells of the adult. The investigators and their collaborators have shown in preliminary studies that the receptor is expressed both in intact tissues from human and murine intestine as well as in several well established cell lines. Additional preliminary evidence from studies on the human T-84 intestinal cell line in monolayer cultures strongly suggests that the receptor is involved in selective endocytosis and transcellular transport of IgG in these adult cells. The investigators propose to use the T-84 cells as model systems to study the detailed features of this transport. In addition, they propose to use model antigens, including rhodamine-conjugated IgG and fusion proteins composed of the Fc region of IgG attached to the urease B protein from H. pylorii, to determine whether the putative transport function of the receptor can be exploited to deliver antigens across the epithelial barrier. In the last portion of the proposed study, they will use the model antigens in in vivo feeding experiments to assess indirectly the possible role of intestinal transport in eliciting an inductive immune response or tolerance.
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