Colonic intraepithelial lymphocytes produce IL-6 in response to resident bacteria to modulate epithelial barrier function

Autor: Kristi Kuhn, Emilie H. Regner, Gaurav Mehta, Jason D. Hendrickson, Alyssa K. Whitney, Eric L. Campbell, Neha Ohri, Sean P. Colgan
Rok vydání: 2016
Předmět:
Zdroj: The Journal of Immunology. 196:208.5-208.5
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.196.supp.208.5
Popis: Interactions between the microbiota and distal gut are important for the maintenance of a healthy immune system. Dysbiosis of colon bacteria has emerged as a likely contributor to diseases that arise at the level of the mucosa. Intraepithelial lymphocytes (IELs) are positioned within the epithelial barrier, and in the small intestine, function to maintain epithelial homeostasis. We hypothesized that IELs of the colon modulate epithelial barrier function through the liberation of cytokines stimulated by interactions with resident bacteria. Our data demonstrate that IL-6 is a major cytokine secreted by colonic IELs in a microbe-dependent fashion. We identify Alistipes species of the phylum Bacteroidetes as candidates to recruit IELs and stimulate their IL-6 secretion. IEL-derived IL-6 is functionally important in the maintenance of the epithelial barrier as IL-6−/− and antibiotic-treated mice were noted to have increased paracellular permeability and closer interaction with luminal bacteria. IL-6 was found to signal in colonic epithelial cells and resulted in increased epithelial barrier integrity and claudin1 expression in model epithelia. Therefore, we conclude that the host microbiota provides a homeostatic role for epithelial barrier function through regulation of IEL derived IL-6.
Databáze: OpenAIRE