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

Ito, Koyu; Nakajima, Akira; Fukushima, Yukinobu; Suzuki, Keiichiro; Sakamoto, Keiko; Hamazaki, Yoko; Ogasawara, Kunio; Minato, Nagahiro; Hattori, Masao

doi:10.1371/journal.pone.0173629

Cited by 18 publications

(24 citation statements)

References 44 publications

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“…The phosphoprotein osteopontin, encoded by the gene Spp-1, is a glycosylated molecule that was originally characterized as part of the rat bone matrix [15, 16], and later shown to induce Th1 responses, promote pathogenic Th17 survival, enhance NKT cell activation of concanavalin A-induced hepatitis, and regulate the homeostasis and function of NK cells [17–21]. A recent publication shows that lack of osteopontin results in reduced TCRγδ IEL, and that this molecule enhances in vitro survival of TCRαβ and TCRγδ IEL [22]. In steady state conditions, iCD8α cells express significant amounts of osteopontin [11], suggesting a potential role for these cells in IEL homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Innate CD8αα+ cells promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation

et al. 2019

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Innate CD8αα + cells, also referred to as iCD8α cells, are TCR-negative intraepithelial lymphocytes (IEL) possessing cytokine and chemokine profiles and functions related to innate immune cells. iCD8α cells constitute an important source of osteopontin in the intestinal epithelium. Osteopontin is a pleiotropic cytokine with diverse roles in bone and tissue remodeling, but also has relevant functions in the homeostasis of immune cells. In this report, we present evidence for the role of iCD8α cells in the homeostasis of TCR-negative NKp46 + NK1.1 + IEL (ILC1-like). We also show that the effect of iCD8α cells on ILC1-like IEL is enhanced in vitro by osteopontin. We show that in the absence of iCD8α cells, the number of NKp46 + NK1.1 + IEL is significantly reduced. These ILC1-like cells are involved in intestinal pathogenesis in the anti-CD40 mouse model of intestinal inflammation. Reduced iCD8α cell numbers results in a milder form of intestinal inflammation in this disease model, whereas treatment with osteopontin increases disease severity. Collectively, our results suggest that iCD8α cells promote survival of NKp46 + NK1.1 + IEL, which significantly impacts the development of intestinal inflammation.

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Section: Introductionmentioning

confidence: 99%

Innate CD8αα+ cells promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation

et al. 2019

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“…2a). To investigate osteopontin production in the IEL compartment, we analyzed Rag-2 −/− mice carrying the Spp-1-EGFP knock-in reporter gene [22]. Whereas NKp46 + NK1.1 + and other CD8α − IEL (NKp46 − NK1.1 lo/− ) presented low GFP staining, most iCD8α cells showed high GFP expression (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…It is important to mention that in order to study innate IEL, our results are based on mice lacking TCR + IEL, and therefore, we do not discard the possibility that some TCR + IEL may be osteopontin producers in wild type mice. Indeed, in steady state conditions, using an osteopontin-GFP reporter system, Hattori’s group showed that TCR + CD8α + IEL represent a source of osteopontin in the intestines of wild type mice [22]. This group also showed that TCRγδ + IEL in vivo are dependent on osteopontin for their survival, whereas in in vitro conditions, both TCRαβ + and γδ + IEL survival is blunted by anti-osteopontin antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…E8 I −/− mice were graciously provided by Dr. Hilde Cheroutre. Spp-1-GFP-Knock-in mice have been previously reported [22]. To homogenize as much as possible the microbiome, all mice obtained from external sources mice were bred in our facility with Rag-2 −/− mice to generate heterozygote mice for both mutations, and from these founders we obtained Spp-1 −/− Rag-2 −/− , E8 I −/− Rag-2 −/− , and Rag-2 −/− Spp-1-GFP-Knock-in mice.…”

Section: Methodsmentioning

confidence: 99%

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Innate CD8αα⁺cells and osteopontin promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation

Olivares–Villagómez¹,

Nazmi²,

Hoek³

et al. 2019

Preprint

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20Innate CD8 + cells, also referred to as iCD8 cells, are TCR-negative intraepithelial 21 lymphocytes (IEL) possessing cytokine and chemokine profiles and functions related to innate 22 immune cells. iCD8 cells constitute an important source of osteopontin in the intestinal 23 epithelium. Osteopontin is a pleiotropic cytokine with diverse roles in bone and tissue 24 remodeling, but also has relevant functions in the homeostasis of immune cells. In this report, we 25 present evidence for the role of iCD8 cells and osteopontin in the homeostasis of TCR-negative 26 NKp46 + NK1.1 + IEL (ILC1-like). We show that in the absence of iCD8 cells, the number of 27 NKp46 + NK1.1 + IEL is significantly reduced. These ILC1-like cells are involved in intestinal 28 pathogenesis in the anti-CD40 mouse model of intestinal inflammation. Reduced iCD8 cell 29 numbers and/or osteopontin expression results in a milder form of intestinal inflammation in this 30 disease model. Collectively, our results suggest that iCD8 cells and osteopontin promote 31 survival of NKp46 + NK1.1 + IEL, which significantly impacts the development of intestinal 32 inflammation. 33 34 42 homeostasis of the intestinal epithelium [4-9]. Lately, it has been recognized that the IEL 43 compartment also harbors TCR neg lymphoid cells with critical roles in mucosal immune 44 responses [3]. The great majority of TCR neg IEL is composed of cells expressing intracellular 45 CD3, which can be divided in CD8 + or CD8 -IEL [10]. TCR neg CD8 + IEL, also referred 46 to as innate CD8 (iCD8) cells, have been previously characterized by our group both in mice

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“…Interestingly, none of the diet interventions led to changes in the gut microbiota composition or diversity, relative to infant formula. Both CGMP and OPN have previously been reported to modulate microbiota composition and play a role in maintaining gut bacterial homeostasis (19,35). In preterm pigs without prenatal inflammation, colostrum feeding also reduced the abundance of Enterococcus spp.…”

Section: Discussionmentioning

confidence: 99%

Gut and immune effects of bioactive milk factors in preterm pigs exposed to prenatal inflammation

Ren

Hui

Goericke-Pesch

et al. 2019

American Journal of Physiology-Gastrointestinal and Liver Physi

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Prenatal inflammation may predispose to preterm birth and postnatal inflammatory disorders such as necrotizing enterocolitis (NEC). Bioactive milk ingredients may help to support gut maturation in such neonates, but mother’s milk is often insufficient after preterm birth. We hypothesized that supplementation with bioactive ingredients from bovine milk [osteopontin (OPN), caseinoglycomacropeptide (CGMP), colostrum (COL)] supports gut, immunity, and NEC resistance in neonates born preterm after gram-negative infection before birth. Using preterm pigs as a model for preterm infants, fetal pigs were given intraamniotic injections of lipopolysaccharide (LPS; 1 mg/fetus) and delivered 3 days later (90% gestation). For 5 days, groups of LPS-exposed pigs were fed formula (FOR), bovine colostrum (COL), or formula enriched with OPN or CGMP. LPS induced intraamniotic inflammation and postnatal systemic inflammation but limited effects on postnatal gut parameters and NEC. Relative to FOR, COL feeding to LPS-exposed pigs showed less diarrhea, NEC severity, reduced gut IL-1β and IL-8 levels, greater gut goblet cell density and digestive enzyme activities, and blood helper T-cell fraction. CGMP improved neonatal arousal and gut lactase activities and reduced LPS-induced IL-8 secretion in intestinal epithelial cells (IECs) in vitro. Finally, OPN tended to reduce diarrhea and stimulated IEC proliferation in vitro. No effects on villus morphology, circulating cytokines, or colonic microbiota were observed among groups. In conclusion, bioactive milk ingredients exerted only modest effects on gut and systemic immune parameters in preterm pigs exposed to prenatal inflammation. Short-term, prenatal exposure to inflammation may render the gut less sensitive to immune-modulatory milk effects. NEW & NOTEWORTHY Prenatal inflammation is a risk factor for preterm birth and postnatal complications including infections. However, from clinical studies, it is difficult to separate the effects of only prenatal inflammation from preterm birth. Using cesarean-delivered preterm pigs with prenatal inflammation, we documented some beneficial gut effects of bioactive milk diets relative to formula, but prenatal inflammation appeared to decrease the sensitivity of enteral feeding. Special treatments and diets may be required for this neonatal population.

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

Cited by 18 publications

References 44 publications

Innate CD8αα+ cells promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation

Innate CD8αα+ cells promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation

Innate CD8αα⁺cells and osteopontin promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation

Gut and immune effects of bioactive milk factors in preterm pigs exposed to prenatal inflammation

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

Cited by 18 publications

References 44 publications

Innate CD8αα+ cells promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation

Innate CD8αα+ cells promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation

Innate CD8αα+cells and osteopontin promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation

Gut and immune effects of bioactive milk factors in preterm pigs exposed to prenatal inflammation

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Innate CD8αα⁺cells and osteopontin promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation