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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Published in:PloS one Vol. 12; no. 3; p. e0173629
Main Authors: Ito, Koyu, Nakajima, Akira, Fukushima, Yuji, Suzuki, Keiichiro, Sakamoto, Keiko, Hamazaki, Yoko, Ogasawara, Kouetsu, Minato, Nagahiro, Hattori, Masakazu
Format: Journal Article
Language:English
Published: United States Public Library of Science 15.03.2017
Public Library of Science (PLoS)
Subjects:
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
Online Access:Get full text
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Summary: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.
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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