title: Paneth cell α-defensins and enteric microbiota in health and disease.
abstract: Antimicrobial peptides are major effectors of innate immunity of multicellular organisms including humans and play a critical role in host defense, and their importance is widely recognized. The epithelium of the intestine is the largest surface area exposed to the outer environment, including pathogens, toxins and foods. The Paneth cell lineage of intestinal epithelial cells produces and secretes α-defensin antimicrobial peptides and functions in innate enteric immunity by removing pathogens and living symbiotically with commensal microbiota to contribute to intestinal homeostasis. Paneth cells secrete α-defensins, HD5 and HD6 in humans and cryptdins in mice, in response to bacterial, cholinergic and other stimuli. The α-defensins have selective activities against bacteria, eliciting potent microbicidal activities against pathogenic bacteria but minimal or no bactericidal activity against commensal bacteria. Therefore, α-defensins regulate the composition of the intestinal microbiota in vivo and play a role in homeostasis of the entire intestine. Recently, relationships between dysbiosis, or abnormal composition of the intestinal microbiota, and diseases such as inflammatory bowel disease and lifestyle diseases including obesity and atherosclerosis have been reported. Because α-defensins regulate the composition of the intestinal microbiota, Paneth cells and their α-defensins may have a key role as one mechanism linking the microbiota and disease.
authors.affiliation: Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Kita-21, Nishi-11, Kita-ku, Sapporo, Hokkaido 001-0021, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Kita-21, Nishi-11, Kita-ku, Sapporo, Hokkaido 001-0021, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakuragi
authors.affiliation: Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Kita-21, Nishi-11, Kita-ku, Sapporo, Hokkaido 001-0021, Japan; Department of Nutrition, Faculty of Nursing and Nutrition, Tenshi College, 3-1-30 Higashi, Kita-13, Higashi-ku, Sapporo, Hokkaido 065-0013, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Takakuwa
authors.affiliation: Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Kita-21, Nishi-11, Kita-ku, Sapporo, Hokkaido 001-0021, Japan.
authors.forename: Tokiyoshi
authors.initials: T
authors.lastname: Ayabe
keywords: Paneth cell; dysbiosis; inflammatory bowel disease; innate immunity; intestinal microbiota; lifestyle disease; α-defensin