The potential role of Osteopontin in the maintenance of commensal bacteria homeostasis in the intestine

Osteopontin (Opn), a multifunctional extracellular matrix protein, is implicated in the pathogenesis of various inflammatory disorders. Under physiologic conditions, its expression is restricted to certain tissues including bone and kidney tubule. However, cellular activation during disease developm...

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Vydané v:	PloS one Ročník 12; číslo 3; s. e0173629
Hlavní autori:	Ito, Koyu, Nakajima, Akira, Fukushima, Yuji, Suzuki, Keiichiro, Sakamoto, Keiko, Hamazaki, Yoko, Ogasawara, Kouetsu, Minato, Nagahiro, Hattori, Masakazu
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 15.03.2017 Public Library of Science (PLoS)
Predmet:	Animal tissues Animals Antigens Bacteria Bacterial Physiological Phenomena Biocompatibility Biology Biology and Life Sciences Blocking antibodies Disease Epithelium Extracellular matrix Fecal microflora Gene Expression Profiling Homeostasis Homeostasis - physiology Immune system Immunoglobulins Immunology Inflammatory bowel disease Inflammatory diseases Intestinal microflora Intestine Intestines Intestines - microbiology Laboratory animals Lamina propria Lymphocytes Lymphocytes T Matrix protein Medicine Medicine and Health Sciences Mice Mice, Transgenic Microbiota Microbiota (Symbiotic organisms) Osteopontin Osteopontin - physiology Pathogenesis Peptides Physiological aspects Rodents Stem cells Survival Survival factor
ISSN:	1932-6203, 1932-6203
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Shrnutí:	Osteopontin (Opn), a multifunctional extracellular matrix protein, is implicated in the pathogenesis of various inflammatory disorders. Under physiologic conditions, its expression is restricted to certain tissues including bone and kidney tubule. However, cellular activation during disease development induces Opn expression in various immune cells. In this study, using Opn-EGFP knock-in (KI) mice we found that CD8α+ T cells in the intestinal tissues, including Peyer's patch, lamina propria and epithelium, express Opn under steady state conditions. Therefore, we examined the role of Opn-expressing CD8α+ T cells in intestinal homeostasis. Interestingly, Opn knockout (KO) mice had altered fecal microflora concordant with a reduction of TCRγδ+ intraepithelial lymphocytes (IELs). Consistent with this result, both treatment with anti-Opn blocking antibody and deficiency of Opn resulted in decreased survival of TCRγδ+ and TCRαβ+ IELs. This data suggests that a possibility that Opn may function as a survival factor for IELs in the intestinal tissue. Collectively, these data suggest the possibility that Opn might regulate the homeostasis of intestinal microflora through maintenance of TCRγδ+ IELs, possibly by support of IEL survival.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceptualization: KI AN K. Suzuki YH NM MH.Formal analysis: KI AN YF K. Suzuki MH.Funding acquisition: KI MH.Investigation: KI YF K. Sakamoto.Methodology: KI AN K. Suzuki YH NM MH.Project administration: KI MH.Supervision: NM MH.Validation: KI AN YF K. Suzuki K. Suzuki MH.Writing – original draft: KI NM MH.Writing – review & editing: KI KO NM MH. Competing Interests: This work was supported by Astellas Pharma Inc. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0173629