ICMI 2015

W.10 Intestinal Mucin-Dendritic Cell Crosstalk in Gut Homeostasis

Wednesday, July 15, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Felipe Melo-Gonzalez , University of Manchester, Manchester, United Kingdom
Thomas Fenton , University of Manchester, Manchester, United Kingdom
David J Thornton , University of Manchester, Manchester, United Kingdom
Mark Travis , University of Manchester, Manchester, United Kingdom
Intestinal dendritic cells (DCs) are essential in sampling luminal antigens and promoting the appropriate immune response to different signals present in the intestinal environment. Intestinal DCs are in close contact with intestinal mucus, a protective barrier mainly composed of the goblet cell-secreted mucin MUC2, which may also play important regulatory functions. Thus, a possibility is that interactions between DCs and mucins modulate DC function, with recent published data suggesting that mucins may trigger anti-inflammatory pathways in DCs. To identify important pathways by which DCs are modulated by intestinal mucins, MUC2 obtained from intestinal cell lines and mouse intestinal mucin was purified and used to treat human monocyte-derived DCs. We now find that expression of pro-inflammatory markers CD86 and CD83 is significantly upregulated on human DCs in the presence of human MUC2 and mouse intestinal mucins, together with the expression of the pro-inflammatory chemokine interleukin 8 (IL-8). Additionally, IL-8 produced by mucin-treated DC is able to enhance neutrophil migration in vitro. Thus, in contrast to recent published results, we find that intestinal mucins are capable of inducing important pro-inflammatory functions in DC. Further investigation is therefore required to explore mucin-DC interactions during health and infection.