Medical College of Wisconsin
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Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity. Mucosal Immunol 2018 Mar;11(2):357-368

Date

08/16/2017

Pubmed ID

28812548

Pubmed Central ID

PMC5815964

DOI

10.1038/mi.2017.55

Scopus ID

2-s2.0-85046085093 (requires institutional sign-in at Scopus site)   146 Citations

Abstract

Interactions between the microbiota and distal gut are important for the maintenance of a healthy intestinal barrier; dysbiosis of intestinal microbial communities 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 they function to maintain epithelial homeostasis. We hypothesized that colon IELs promote epithelial barrier function through the expression of cytokines in response to interactions with commensal bacteria. Profiling of bacterial 16S ribosomal RNA revealed that candidate bacteria in the order Bacteroidales are sufficient to promote IEL presence in the colon that in turn produce interleukin-6 (IL-6) in a MyD88 (myeloid differentiation primary response 88)-dependent manner. IEL-derived IL-6 is functionally important in the maintenance of the epithelial barrier as IL-6-/- mice were noted to have increased paracellular permeability, decreased claudin-1 expression, and a thinner mucus gel layer, all of which were reversed by transfer of IL-6+/+ IELs, leading to protection of mice in response to Citrobacter rodentium infection. Therefore, we conclude that microbiota provide a homeostatic role for epithelial barrier function through regulation of IEL-derived IL-6.

Author List

Kuhn KA, Schulz HM, Regner EH, Severs EL, Hendrickson JD, Mehta G, Whitney AK, Ir D, Ohri N, Robertson CE, Frank DN, Campbell EL, Colgan SP

Author

Emilie Regner MD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bacteroidaceae
Cell Membrane Permeability
Citrobacter rodentium
Colon
Dysbiosis
Enterobacteriaceae Infections
Gastrointestinal Microbiome
Homeostasis
Immunity, Innate
Interleukin-6
Intestinal Mucosa
Intraepithelial Lymphocytes
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
RNA, Ribosomal, 16S
Symbiosis