TY - JOUR
T1 - Intestinal mucin activates human dendritic cells and IL-8 production in a glycan-specific manner
AU - Melo-Gonzalez, Felipe
AU - Fenton, Thomas M.
AU - Forss, Cecilia
AU - Smedley, Catherine
AU - Goenka, Anu
AU - MacDonald, Andrew S.
AU - Thornton, David J.
AU - Travis, Mark A.
N1 - Publisher Copyright:
© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Cross-talk between different components of the intestinal barrier and the immune system may be important in maintaining gut homeostasis. A crucial part of the gut barrier is the mucus layer, a cross-linked gel on top of the intestinal epithelium that consists predominantly of the mucin glycoprotein MUC2. However, whether the mucin layer actively regulates intestinal immune cell responses is not clear. Because recent evidence suggests that intestinal dendritic cells (DCs) may be regulated by the mucus layer, we purified intestinal mucin, incubated it with human DCs, and determined the functional effects. Here we show that expression of the chemokine IL-8 and co-stimulatory DC markers CD86 and CD83 are significantly up-regulated on human DCs in the presence of intestinal mucins. Additionally, mucin-exposed DCs promoted neutrophil migration in an IL-8 – dependent manner. The stimulatory effects of mucins on DCs were not due to mucin sample contaminants such as lipopolysaccharide, DNA, or contaminant proteins. Instead, mucin glycans are important for the pro-inflammatory effects on DCs. Thus, intestinal mucins are capable of inducing important pro-inflammatory functions in DCs, which could be important in driving inflammatory responses upon intestinal barrier damage.
AB - Cross-talk between different components of the intestinal barrier and the immune system may be important in maintaining gut homeostasis. A crucial part of the gut barrier is the mucus layer, a cross-linked gel on top of the intestinal epithelium that consists predominantly of the mucin glycoprotein MUC2. However, whether the mucin layer actively regulates intestinal immune cell responses is not clear. Because recent evidence suggests that intestinal dendritic cells (DCs) may be regulated by the mucus layer, we purified intestinal mucin, incubated it with human DCs, and determined the functional effects. Here we show that expression of the chemokine IL-8 and co-stimulatory DC markers CD86 and CD83 are significantly up-regulated on human DCs in the presence of intestinal mucins. Additionally, mucin-exposed DCs promoted neutrophil migration in an IL-8 – dependent manner. The stimulatory effects of mucins on DCs were not due to mucin sample contaminants such as lipopolysaccharide, DNA, or contaminant proteins. Instead, mucin glycans are important for the pro-inflammatory effects on DCs. Thus, intestinal mucins are capable of inducing important pro-inflammatory functions in DCs, which could be important in driving inflammatory responses upon intestinal barrier damage.
UR - http://www.scopus.com/inward/record.url?scp=85048039587&partnerID=8YFLogxK
U2 - 10.1074/jbc.M117.789305
DO - 10.1074/jbc.M117.789305
M3 - Article
C2 - 29581231
AN - SCOPUS:85048039587
SN - 0021-9258
VL - 293
SP - 8543
EP - 8553
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 22
ER -