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Fucoidan prevent murine autoimmune diabetes via suppression TLR4-signaling pathways, regulation DC/Treg induced immune tolerance and improving gut microecology.

ABSTRACT: Background:This study was to investigate the effect and its possible mechanism of fucoidan on the development of spontaneous autoimmune diabetes in non-obese diabetic (NOD) mice. Methods:7-week-old NOD mice were randomly divided into three groups: control group, low-dose (300?mg/kg) and high-dose (600?mg/kg) fucoidan-treatment groups. After 5?weeks of treatment, 10 mice per group were randomly selected to be sacrificed after feces collection. The remaining 12 mice per group were fed until 26?weeks of age to assess the incidence of diabetes. Results:Treatment with fucoidan increased serum insulin level, delayed the onset and decreased the development of diabetes in NOD mice. Fucoidan reduced the levels of strong Th1 proinflammatory cytokines, but induced Th2-bias ed. cytokine response. And dentridic cells (DCs) in fucoidan treatment group were characterized as low expression of MHC class II and CD86 molecules. TLR4 expressions and the downstream molecules in pancreas were down-regulated in fucoidan-treated groups. There were significant differences in the composition of gut flora between NOD control group and fucoidan group. Lactobacillus and Akkermansia were significantly enriched in fucoidan group. Conclusions:Fucoidan could prevent the development of autoimmune diabetes in NOD mice via regulating DC/Treg induced immune tolerance, improving gut microecology, down-regulating TLR4 signaling pathway, and maintaining pancreatic internal environment.

SUBMITTER: Xue M

PROVIDER: S-EPMC6916240 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Fucoidan prevent murine autoimmune diabetes via suppression TLR4-signaling pathways, regulation DC/Treg induced immune tolerance and improving gut microecology.

Xue Meilan M Liang Hui H Ji Xinqiang X Liu Ying Y Ge Yinlin Y Hou Lin L Sun Ting T

Nutrition & metabolism 20191216

<h4>Background</h4>This study was to investigate the effect and its possible mechanism of fucoidan on the development of spontaneous autoimmune diabetes in non-obese diabetic (NOD) mice.<h4>Methods</h4>7-week-old NOD mice were randomly divided into three groups: control group, low-dose (300 mg/kg) and high-dose (600 mg/kg) fucoidan-treatment groups. After 5 weeks of treatment, 10 mice per group were randomly selected to be sacrificed after feces collection. The remaining 12 mice per group were f ...[more]

PMID: 31889967

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Project description:BackgroundImmune homeostasis requires fully functional Tregs with a stable phenotype to control autoimmunity. Although IL-34 is a cytokine first described as mainly involved in monocyte cell survival and differentiation, we recently described its expression by CD8+ Tregs in a rat model of transplantation tolerance and by activated FOXP3+ CD4+ and CD8+ Tregs in human healthy individuals. However, its role in autoimmunity and potential in human diseases remains to be determined.MethodsWe generated Il34-/- rats and using both Il34-/- rats and mice, we investigated their phenotype under inflammatory conditions. Using Il34-/- rats, we further analyzed the impact of the absence of expression of IL-34 for CD4+ Tregs suppressive function. We investigated the potential of IL-34 in human disease to prevent xenogeneic GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, taking advantage of a biocollection, we investigated the correlation between presence of IL-34 in the serum and kidney transplant rejection.ResultsHere we report that the absence of expression of IL-34 in Il34-/- rats and mice leads to an unstable immune phenotype, with production of multiple auto-antibodies, exacerbated under inflammatory conditions with increased susceptibility to DSS- and TNBS-colitis in Il34-/- animals. Moreover, we revealed the striking inability of Il34-/- CD4+ Tregs to protect Il2rg-/- rats from a wasting disease induced by transfer of pathogenic cells, in contrast to Il34+/+ CD4+ Tregs. We also showed that IL-34 treatment delayed EAE in mice as well as GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, we show that presence of IL-34 in the serum is associated with a longer rejection-free period in kidney transplanted patients.ConclusionAltogether, our data emphasize on the crucial necessity of IL-34 for immune homeostasis and for CD4+ Tregs suppressive function. Our data also shows the therapeutic potential of IL-34 in human transplantation and auto-immunity.Highlights-Absence of expression of IL-34 in Il34-/- rats and mice leads to an unstable immune phenotype, with a production of multiple auto-antibodies and exacerbated immune pathology under inflammatory conditions. -Il34-/- CD4+ Tregs are unable to protect Il2rg-/- rats from colitis induced by transfer of pathogenic cells. -IL-34 treatment delayed EAE in mice, as well as acute GVHD and human skin allograft rejection in immune-humanized immunodeficient NSG mice.

Dataset Information

Fucoidan prevent murine autoimmune diabetes via suppression TLR4-signaling pathways, regulation DC/Treg induced immune tolerance and improving gut microecology.

Publications

Fucoidan prevent murine autoimmune diabetes via suppression TLR4-signaling pathways, regulation DC/Treg induced immune tolerance and improving gut microecology.

Similar Datasets

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