These results suggest that IL-10 production by ManLAM-treated B cells contributes to keeping the balance between CD4<sup>+</sup> T cell subsets and protect mice from DSS-induced IBD.
The data suggest that endogenous T cell-derived opioids might reduce inflammation-induced abdominal pain in inflammatory bowel diseases associated with homozygous "loss of function mutations" in interleukin-10.
The interleukin-10 knockout (IL-10 KO) mouse is a well-known animal model of IBD that develops spontaneous intestinal inflammation resembling Crohns disease.
SNPs rs1800896, rs3024505 (IL-10); rs11209026 (IL23R); rs2066844, rs2066845 (NOD-2), and rs2241880 (ATG16L1) were assessed in 93 patients with IBD and 200 healthy controls by hybridization probes and quantitative PCR.
These results identify a regulatory interaction between IL-10 and PGE2, dysregulation of which may drive aberrant Mφ activation and impaired host defense contributing to IBD pathogenesis.
Here, we show that in a murine inflammatory bowel disease (IBD) model based on macrophage-restricted interleukin-10 (IL-10) receptor deficiency (<i>Cx3cr1<sup>Cre</sup>:Il10ra<sup>fl/fl</sup></i> mice), proinflammatory mutant gut macrophages cause severe spontaneous colitis resembling the condition observed in children carrying IL-10R mutations.
Consistent with the PBMC data, both <i>L. fermentum</i> KBL374- and KBL375-treated DSS mice demonstrated decreased Th1-, Th2-, and Th17-related cytokine levels and increased IL-10 in the colon compared with the DSS control mice.Administration of <i>L. fermentum</i> KBL374 or KBL375 to mice increased the CD4+CD25+Foxp3+Treg cell population in mesenteric lymph nodes.Additionally, <i>L. fermentum</i> KBL374 or KBL375 administration reshaped and increased the diversity of the gut microbiota.In particular, <i>L. fermentum</i> KBL375 increased the abundance of beneficial microorganisms, such as <i>Lactobacillus</i> spp. and <i>Akkermansia</i> spp.Both <i>L. fermentum</i> KBL374 and KBL375 may alleviate inflammatory diseases, such as inflammatory bowel disease, in the gut by regulating immune responses and altering the composition of gut microbiota.
We observed that C3H ASF and 129 ASF IL-10 are more sensitive towardB7 600 μg/mL vitamin B<sub>3</sub> and 1,200 μg/mL vitamin C. The lowest growth rate and viability for all types of organoids was with 1,200 μg/mL vitamin C. From quantitative polymerase chain reaction analysis (qPCR analysis), MUC2 was upregulated for 129 ASF and C3H Conv when exposed to 600 μg/mL and 1,200 μg/mL vitamin C. It suggests that large amounts of glycoprotein may be produced after adding high concentrations of vitamin C. Since inflammatory bowel disease has low level of MUC2, this finding may be helpful in restoring mucosal health by upregulating the MUC2 gene while altering patient's microbiota (Sibila et al., Annals of the American Thoracic Society, 2016).
Mutations in interleukin-10 and its receptors cause infantile inflammatory bowel disease (IBD), a hyperinflammatory disorder characterized by severe, treatment-refractory colitis, multiple abscesses, and enterocutaneous fistulas.
We investigated two main types of Tregs, the CD4+FOXP3+ and IL-10+ Tr1, in pediatric subjects with inflammatory bowel disease (IBD) both at diagnosis and after the clinical remission.
Employing a TNFα-driven murine inflammatory bowel disease (IBD) model (TNF<sup>ΔARE/+</sup>), which mirrors the Treg expansion and transmural ileitis seen in Crohn's disease, we demonstrate that the TNFα-mediated loss of Treg suppressive function coincides with induction of a specific miRNA, miR-106a in both humans and mice, via NFκB promoter binding to suppress post-transcriptional regulation of IL-10 release.
Moreover, in Il10-deficient mice with inflammatory bowel disease and normal kidney function, plasma FGF23 was elevated and normalized upon TNF neutralization.
<i>Enterococcus faecalis</i> is a resident member of the human intestinal core microbiota that has been linked to the pathogenesis of IBD and induces chronic colitis in susceptible monoassociated IL-10-deficient (IL-10<sup>-/-</sup>) mice.
The apolipoprotein A-I (APOA1) mimetic 4F mitigated disease in both the Cox2 MKO/CCHF and piroxicam-accelerated Il10-/- models of inflammatory bowel disease (IBD) and reduced elevated levels of pro-inflammatory mediators in tissue and plasma.
This is the first study investigating consequences of hydromorphone in both dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis [IL-10 knockout (IL-10-/-)] mouse model of IBD.
These data indicate that butyrate controls the capacity of T cells in the induction of colitis by differentially regulating Th1 and Th17 cell differentiation and promoting IL-10 production, providing insights into butyrate as a potential therapeutic for the treatment of inflammatory bowel disease.
A better understanding of how IL-10 exerts its suppressive function may allow identification of individuals with suboptimal IL-10 function among the heterogeneous population of IBD patients.
Collectively, our work identifies Shp2 as a detrimental factor for intestinal immune homeostasis and hopefully will be helpful in the future exploitation of IL-10 immunotherapy for IBD.