Dataset Information

CD5 Controls Gut Immunity by Shaping the Cytokine Profile of Intestinal T Cells.

ABSTRACT: CD5 is constitutively expressed on all T cells and is a negative regulator of lymphocyte function. However, the full extent of CD5 function in immunity remains unclear. CD5 deficiency impacts thymic selection and extra-thymic regulatory T cell generation, yet CD5 knockout was reported to cause no immune pathology. Here we show that CD5 is a key modulator of gut immunity. We generated mice with inducible CD5 knockdown (KD) in the autoimmune-prone nonobese diabetic (NOD) background. CD5 deficiency caused T cell-dependent wasting disease driven by chronic gut immune dysregulation. CD5 inhibition also exacerbated acute experimental colitis. Mechanistically, loss of CD5 increased phospho-Stat3 levels, leading to elevated IL-17A secretion. Our data reveal a new facet of CD5 function in shaping the T cell cytokine profile.

SUBMITTER: Schuster C

PROVIDER: S-EPMC9201032 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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CD5 Controls Gut Immunity by Shaping the Cytokine Profile of Intestinal T Cells.

Schuster Cornelia C Kiaf Badr B Hatzihristidis Teri T Ruckdeschel Anna A Nieves-Bonilla Janice J Ishikawa Yuki Y Zhao Bin B Zheng Peilin P Love Paul E PE Kissler Stephan S

Frontiers in immunology 20220602

CD5 is constitutively expressed on all T cells and is a negative regulator of lymphocyte function. However, the full extent of CD5 function in immunity remains unclear. CD5 deficiency impacts thymic selection and extra-thymic regulatory T cell generation, yet CD5 knockout was reported to cause no immune pathology. Here we show that CD5 is a key modulator of gut immunity. We generated mice with inducible CD5 knockdown (KD) in the autoimmune-prone nonobese diabetic (NOD) background. CD5 deficiency ...[more]

PMID: 35720357

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Project description:Antibiotic resistance of pathogens, which is caused by the abuse of in-feed antibiotics, threatens the sustainable development of livestock production. The present study aimed to investigate the efficiency of porcine intestinal antimicrobial peptide (PIAP) as an alternative to in-feed antibiotics in terms of growth performance, intestinal morphology, digestive enzymes and immunity, and microbiota community of the post-weaning piglets. A total of 204 piglets (Duroc × Landrace × Yorkshire, weaned at 28 d age) with a similar body weight of 7.97 ± 1.04 kg were randomly allocated to 4 groups (51 piglets per group): (1) control group: basal diet; (2) AB group: antibiotic, basal diet + chlortetracycline (1000 mg/kg from d 1 to 24; 500 mg/kg from d 25 to 37); (3) P1 group: basal diet + a relatively low dose of PIAP (400 mg/kg from d 1 to 24; 300 mg/kg from d 25 to 37); (4) P2 group, basal diet + a relatively high dose of PIAP (600 mg/kg from d 1 to 24; 500 mg/kg from d 25 to 37). The results showed that serum indicators of hepatocyte damage and relative organ weight were not affected by these treatments (P > 0.05). Compared with the AB treatment, the P1 treatment remarkably decreased jejunal crypt depth and increased jejunal and ileal villus height:crypt depth ratio (P < 0.05). The values of jejunal maltase, lactase, sucrase, intestinal alkaline phosphatase, and secretory immunoglobulin A (SIgA) in the P1 group were sharply increased compared with those in the control and P2 groups (P < 0.05). Compared with the control group, the P1 group decreased serum concentrations of D-lactate, diamine oxidase, and endotoxin (P < 0.05), and increased the abundance of Lactobacillus reuteri (P < 0.05) in the colonic feces. Furthermore, there was a positive correlation between the abundance of L. reuteri and the concentrations of maltase, lactase, sucrase, and SIgA (P < 0.05). Collectively, dietary supplementation with a relatively low dose of PIAP (400 mg/kg from d 1 to 24; 300 mg/kg from d 25 to 37) demonstrates beneficial effects on intestinal morphology, digestive enzymes, immunity, and permeability by shaping the gut microbiota composition in weaned piglets. This study will provide a valuable reference for using PIAP as an in-feed antibiotic alternative in swine production.

Project description:Background and aimsGut dysbiosis and abnormal cytokine profiles are common in cirrhosis. This study aimed to evaluate the correlations between them.MethodsIn the blood plasma of cirrhosis patients and controls, 27 cytokines were examined using a multiplex assay. The plasma levels of nitrites (stable metabolites of the endothelial dysfunction biomarker nitric oxide) and lipopolysaccharide (LPS) were examined. The fecal microbiota was assessed by 16S rRNA gene sequencing.ResultsLevels of IL-1b, IL-2, IL-6, IL-13, IP-10, IFN-g, TNF-a, LPS, and nitrites were higher in cirrhosis patients than in controls, while levels of IL-4, IL-7, and PDGF-BB were lower. The LPS level was directly correlated with the levels of IL-1b, IL1-Ra, IL-9, IL-17, PDGF-BB, IL-6, TNF-a, and nitrites. The nitrite level was significantly directly correlated with the levels of TNF-a, GM-CSF, IL-17, and IL-12, and inversely correlated with the IL-7 level. TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes, Enterobacteriaceae, Veillonellaceae, and Klebsiella, while inversely correlated with the abundance of Firmicutes, Clostridia, and Subdoligranulum. IFN-g levels were directly correlated with the abundance of Bacteroidaceae, Lactobacillaceae, Bacteroides, and Megasphaera, and inversely correlated with the abundance of Verrucomicrobiota, Akkermansiaceae, Coriobacteriaceae, Akkermansia, Collinsella, and Gemella. IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister. IL-6 levels were directly correlated with the abundance of Enterobacteriaceae, hepatic encephalopathy, and ascites severity, and inversely correlated with the abundance of Peptostreptococcaceae, Streptococcaceae, and Streptococcus.ConclusionsThe abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.

Dataset Information

CD5 Controls Gut Immunity by Shaping the Cytokine Profile of Intestinal T Cells.

Publications

CD5 Controls Gut Immunity by Shaping the Cytokine Profile of Intestinal T Cells.

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