scholarly journals Impaired 25-hydroxylation of vitamin D in liver injury suppresses intestinal Paneth cell defensins, leading to gut dysbiosis and liver fibrogenesis

2020 ◽  
Vol 319 (6) ◽  
pp. G685-G695
Author(s):  
Pengfei Wu ◽  
Ruofei Zhang ◽  
Mei Luo ◽  
Tianci Zhang ◽  
Lisha Pan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Innate Immunity ◽  
Small Intestine ◽  
Liver Diseases ◽  
Paneth Cell ◽  
Intestinal Immunity ◽  
Cell Functions ◽  
Gut Dysbiosis ◽  
Liver Fibrogenesis

Vitamin D deficiency is coprevalent with various liver diseases, indicating the role of vitamin D in maintaining liver homeostasis. In this study, we observed that the hepatic 25-hydroxylation of VD is critical for intestinal innate immunity through VD signaling in the small intestine for maintaining Paneth cell functions. Conversely, failure of biogenesis of VD in the liver impairs intestinal immunity, leading to gut dysbiosis and endotoxemia, which promotes liver fibrogenesis.

scholarly journals Vitamin D signaling maintains intestinal innate immunity and gut microbiota: potential intervention for metabolic syndrome and NAFLD

2020 ◽  
Vol 318 (3) ◽  
pp. G542-G553 ◽  
Author(s):  
Yilan Zeng ◽  
Mei Luo ◽  
Liwei Pan ◽  
Yuan Chen ◽  
Siqi Guo ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Vitamin D ◽  
Innate Immunity ◽  
Small Intestine ◽  
Bacterial Translocation ◽  
Paneth Cell ◽  
Distal Region ◽  
Dietary Vitamin ◽  
Experimental Investigations ◽  
Vitamin D Signaling

A lack of sunlight exposure, residence in the northern latitudes, and dietary vitamin D insufficiency are coprevalent with metabolic syndrome (MetS), Type 2 diabetes (T2D), and nonalcoholic fatty liver diseases (NAFLD), implying a potential causality and underlying mechanism. Whether vitamin D supplementation or treatment can improve these disorders is controversial, in part, because of the absence of large-scale trials. Experimental investigations, on the other hand, have uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin that maintained calcium homeostasis. While the large intestine harbors massive numbers of microbes, the small intestine has a minimal quantity of bacteria, indicating the existence of a gating system located in the distal region of the small intestine that may restrain bacterial translocation to the small intestine. Vitamin D receptor (VDR) was found to be highly expressed at the distal region of small intestine, where the vitamin D signaling promotes innate immunity, including the expression of α-defensins by Paneth cells, and maintains the intestinal tight junctions. Thus, a new hypothesis is emerging, indicating that vitamin D deficiency may impair the intestinal innate immunity, including downregulation of Paneth cell defensins, leading to bacterial translocation, endotoxemia, systemic inflammation, insulin resistance, and hepatic steatosis. Here, we review the studies for vitamin D for innate immunity and metabolic homeostasis, and we outline the clinical trials of vitamin D for mitigating MetS, T2D, and NAFLD.

Role of glycosphingolipid-enriched microdomains in innate immunity: Microdomain-dependent phagocytic cell functions

2008 ◽  
Vol 1780 (3) ◽  
pp. 383-392 ◽  
Author(s):  
Fumiko Yoshizaki ◽  
Hitoshi Nakayama ◽  
Chihiro Iwahara ◽  
Kenji Takamori ◽  
Hideoki Ogawa ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Phagocytic Cell ◽  
Cell Functions

scholarly journals Innate immune deficiencies in patients with COVID-19

2021 ◽  
Author(s):  
Marine Peyneau ◽  
Vanessa Granger ◽  
Paul-Henri Wicky ◽  
Dounia Khelifi-Touhami ◽  
Jean-François Timsit ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Myeloid Cell ◽  
Innate Immune ◽  
Activation Markers ◽  
Icu Patients ◽  
Cell Functions ◽  
Hla Dr ◽  
Immune Deficiencies ◽  
Severe Infections

AbstractCOVID-19 can cause acute respiratory distress syndrome (ARDS), leading to death in a significant number of individuals. Evidence of a strong role of the innate immune system is accumulating, but the precise cells and mechanism involved remain unclear. In this study, we investigated the links between circulating innate phagocyte phenotype and functions and severity in COVID-19 patients. Eighty-four consecutive patients were included, 44 of which were in intensive care units (ICU). We performed an in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, myeloid cell functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Resulting parameters were linked to disease severity and prognosis. Both ICU and non-ICU patients had circulating neutrophils and monocytes with an activated phenotype, as well as elevated concentrations of soluble activation markers (calprotectin, myeloperoxidase, neutrophil extracellular traps, MMP9, sCD14) in their plasma. ICU patients were characterized by increased CD10low CD13low immature neutrophils, LOX-1+ and CCR5+ immunosuppressive neutrophils, and HLA-DRlow CD14low downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity and poor outcome. Moreover, neutrophils and monocytes of ICU patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Our study reveals a marked dysregulation of innate immunity in COVID-19 patients, which was correlated with severity and prognosis. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.One Sentence SummaryOur study reveals a marked dysregulation of innate immunity in COVID-19 patients, which correlates with severity and prognosis.

Paneth Cells and their Antimicrobials in Intestinal Immunity

2018 ◽  
Vol 24 (10) ◽  
pp. 1121-1129 ◽  
Author(s):  
Timon E. Adolph ◽  
Lisa Mayr ◽  
Felix Grabherr ◽  
Herbert Tilg
Keyword(s):  
Intestinal Inflammation ◽  
Paneth Cell ◽  
Paneth Cells ◽  
Secretory Cells ◽  
Intestinal Epithelial ◽  
Intestinal Immunity ◽  
Susceptibility To Infection ◽  
Cell Functions ◽  
Bowel Diseases ◽  
Initial Description

Since the initial description of granular-rich small-intestinal crypt-based epithelial cells in 1872, today referred to as Paneth cells, a plethora of recent studies underlined their function in intestinal homeostasis. Paneth cells are evolutionary conserved highly secretory cells that produce antimicrobials to control gut microbial communities. Moreover, Paneth cells emerged as stem cell regulators that translate environmental cues into intestinal epithelial responses. Paneth cell disturbances may instigate intestinal inflammation and provide susceptibility to infection. Altered Paneth cell functions have been associated with a variety of inflammatory disease models and were linked to human intestinal disease processes including inflammatory bowel diseases such as Crohn´s disease and ulcerative colitis. This review summarizes our current understanding of Paneth cells and their antimicrobials in health and disease.

Bile Acids Regulate Intestinal Paneth Cell Functions and Contribute to Gut Dysbiosis Induced by High Fat Feeding

2017 ◽  
Vol 152 (5) ◽  
pp. S184
Author(s):  
Hui Zhou ◽  
Merritt Gillilland ◽  
Jun Gao ◽  
Shi-Yi Zhou ◽  
Guanpo Zhang ◽  
...  
Keyword(s):  
Bile Acids ◽  
Paneth Cell ◽  
High Fat ◽  
Cell Functions ◽  
Gut Dysbiosis ◽  
Fat Feeding

Calcium transport in small intestine during early development: role of vitamin D

1980 ◽  
Vol 239 (6) ◽  
pp. G473-G479 ◽  
Author(s):  
B. P. Halloran ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Small Intestine ◽  
Early Development ◽  
Calcium Transport ◽  
Plasma Concentrations ◽  
Suckling Period ◽  
Dihydroxyvitamin D3 ◽  
Weanling Rats ◽  
Normal Males

To define the role of vitamin D in calcium transport in the intestine during early development, female weanling rats were placed on vitamin D-replete or vitamin D-deficient diets, grown to maturity, and mated with normal males. Pups born to vitamin D-replete and vitamin D-deficient mothers were killed at various times after parturition, and calcium transport in the small intestine as well as the concentrations of calcium and phosphate in the plasma were measured. Transport of calcium in pups from vitamin D-replete and vitamin D-deficient litters was identical at 3 and 14 days postpartum but was threefold greater in pups from vitamin D-replete litters at weaning and 3 wk postweaning. 1,25-dihydroxyvitamin D3 had no effect on calcium transport at 14 days postpartum but did induce transport at weaning. Plasma concentrations of calcium at 3 days postpartum were nearly normal but decreased during the suckling period from 10.3 mg/100ml to 7.2 mg/100 ml in vitamin D-deficient rats. These results suggest that calcium transport in the intestine during early development is not mediated by vitamin D but that a vitamin D-sensitive transport system develops late in the suckling period.

scholarly journals Maternal Vitamin D Level Is Associated with Viral Toll-Like Receptor Triggered IL-10 Response but Not the Risk of Infectious Diseases in Infancy

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Sui-Ling Liao ◽  
Shen-Hao Lai ◽  
Ming-Han Tsai ◽  
Man-Chin Hua ◽  
Kuo-Wei Yeh ◽  
...  
Keyword(s):  
Vitamin D ◽  
Innate Immunity ◽  
Infectious Diseases ◽  
Cord Blood ◽  
Vitamin D Status ◽  
Toll Like Receptor ◽  
Immune Development ◽  
Maternal Vitamin ◽  
Pregnant Mothers

Reports on the effect of prenatal vitamin D status on fetal immune development and infectious diseases in childhood are limited. The aim of this study was to investigate the role of maternal and cord blood vitamin D level in TLR-related innate immunity and its effect on infectious outcome. Maternal and cord blood 25 (OH)D level were examined from 372 maternal-neonatal pairs and their correlation with TLR-triggered TNF-α, IL-6, and IL-10 response at birth was assessed. Clinical outcomes related to infection at 12 months of age were also evaluated. The result showed that 75% of the pregnant mothers and 75.8% of the neonates were vitamin deficient. There was a high correlation between maternal and cord 25(OH)D levels (r=0.67,p<0.001). Maternal vitamin D level was inversely correlated with IL-10 response to TLR3 (p=0.004) and TLR7-8 stimulation (p=0.006). However, none of the TLR-triggered cytokine productions were associated with cord 25(OH)D concentration. There was no relationship between maternal and cord blood vitamin D status with infectious diseases during infancy. In conclusion, our study had shown that maternal vitamin D, but not cord vitamin D level, was associated with viral TLR-triggered IL-10 response.

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