Vitamin D counteracts fibrogenic TGF-β signalling in human hepatic stellate cells both receptor-dependently and independently

Beilfuss, A; Sowa, Jan-Peter; Sydor, Svenja; Beste, Mechthild; Bechmann, Lars P.; Schlattjan, Martin; Syn, Wing–Kin; Wedemeyer, Inga; Máthé, Z.; Jochum, Christoph; Gerken, Guido; Gieseler, Robert K.; Canbay, Ali

doi:10.1136/gutjnl-2014-307024

Cited by 125 publications

(112 citation statements)

References 36 publications

(46 reference statements)

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“…In all groups, female patients exceeded the number of male patients. HCs were younger than NAFL patients, as seen also in other human studies (16,17). In Germany, NAFLD has a high prevalence (∼20-35%), with an increase in elderly people who also have a higher frequency of metabolic disorders (1).…”

Section: Cohort Characteristicsmentioning

confidence: 64%

Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis Is Marked by a Higher Frequency of Th17 Cells in the Liver and an Increased Th17/Resting Regulatory T Cell Ratio in Peripheral Blood and in the Liver

Rau

Schilling

Meertens

et al. 2016

The Journal of Immunology

228

239

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Nonalcoholic fatty liver disease is increasing in prevalence. It can be subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Five to twenty percent of cases progress from NAFL to NASH. Increased hepatic Th17 cells and IL-17 expression were observed in NASH mice and patients, respectively. We analyzed CD4+ effector T cells and regulatory T cells (Tregs) from peripheral blood and livers of NAFL and NASH patients. A total of 51 NAFL patients, 30 NASH patients, 31 nonalcoholic fatty liver disease patients (without histology), and 43 healthy controls were included. FACS analysis was performed on PBMCs and intrahepatic lymphocytes. Compared with healthy controls, a lower frequency of resting Tregs (rTregs; CD4+CD45RA+CD25++) and higher frequencies of IFN-γ+ and/or IL-4+ cells were detected among CD4+ T cells of peripheral blood in NASH, and to a lesser degree in NAFL. In hepatic tissue, NAFL to NASH progression was marked by an increase in IL-17+ cells among intrahepatic CD4+ T cells. To define immunological parameters in peripheral blood to distinguish NAFL from NASH, we calculated different ratios. Th17/rTreg and Th2/rTreg ratios were significantly increased in NASH versus NAFL. The relevance of our findings for NASH pathogenesis was highlighted by the normalization of all of the changes 1 y after bariatric surgery. In conclusion, our data indicate that NAFL patients show changes in their immune cell profile compared with healthy controls. NAFL to NASH progression is marked by an increased frequency of IL-17+ cells among intrahepatic CD4+ T cells and higher Th17/rTreg and Th2/rTreg ratios in peripheral blood.

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Section: Cohort Characteristicsmentioning

confidence: 64%

Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis Is Marked by a Higher Frequency of Th17 Cells in the Liver and an Increased Th17/Resting Regulatory T Cell Ratio in Peripheral Blood and in the Liver

Rau

Schilling

Meertens

et al. 2016

The Journal of Immunology

228

239

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“…In addition, Vit D deficiency has been implicated in various disorders like coronary heart disease, hypertension, myocardial infarction, stroke, and cancers of the colon, breast, prostate, and lymphoma [19,20,21,22,23,24]. Serum Vit D is also reduced in patients with non-alcoholic fatty liver disease [25]. Surprisingly, there are multiple studies linking non-alcoholic fatty liver disease to CD [26,27,28].…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Polyautoimmunity among Patients with Celiac Disease: A Cross-Sectional Survey

et al. 2015

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Aim: To define the prevalence of polyautoimmunity (PAI) among celiac disease (CD) patients and to compare clinical and laboratory features of CD patients with or without PAI in order to determine the risk factors for PAI in CD. Material and Method: Patients diagnosed with CD in our clinic between 2007 and 2014 with at least 1 year of follow-up were retrospectively evaluated. Totally 145 patients were included in the study. Information on patient demographics and laboratory data were obtained from patient records. The study participants were divided into 2 groups. Group 1 was the CD-alone group consisting of patients without any other autoimmune diseases (AIDs), while group 2 was the PAI group consisting of patients with accompanying one or more AIDs. Results: The mean age of 145 CD patients (106 female and 39 male) included in the study was 37.2 ± 12.3 years. Of the 145 patients included, 48 (33.1%) were in the PAI group. When two groups were compared with each other in terms of the demographic features and laboratory data, the following were identified as risk factors for PAI: female gender, family history for AIDs, antigliadin IgG positivity, vitamin D deficiency, antinuclear antibody positivity ≥1/80 titer and having any musculoskeletal disease. Conclusion: To the best of our knowledge, this is one of the largest studies in the literature on CD patients for the PAI prevalence and related risk factors. Identification of the risk factors in early stages is important to explore PAI among CD patients. Larger, prospective studies are warranted about the risk factors and autoimmune characteristics of CD.

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“…AMPK, 5' adenosine monophosphate-activated protein kinase; Ask-1, apoptosis signal-regulating kinase 1 (Ask-1 is also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5)); CCL2 chemokine (C-C motif) ligand 2 (CCL2 is also referred to as monocyte chemoattractant protein 1 (MCP1)); CCR, chemokine receptor; FGF-21, fibroblast growth factor-21; JNK, C-Jun-Nterminal kinase; mTOR, mechanistic target of rapamycin/ mammalian target of rapamycin; PPARs, peroxisome activated proliferated receptors α, γ and δ; NF-kB, nuclear factor-kB; Nrf 2, nuclear factor (erythroid-derived 2)-like 2; FXR, farnesoid X receptor; SREBPs, sterol regulatory element binding protein. Hepatic inflammation and fibrosis 79,80 .…”

Section: Glossary Termsmentioning

confidence: 99%

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease

2017

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Vitamin D counteracts fibrogenic TGF-β signalling in human hepatic stellate cells both receptor-dependently and independently

Abstract: VD may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR may influence the response to VD treatment.

Cited by 125 publications

References 36 publications

Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis Is Marked by a Higher Frequency of Th17 Cells in the Liver and an Increased Th17/Resting Regulatory T Cell Ratio in Peripheral Blood and in the Liver

Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis Is Marked by a Higher Frequency of Th17 Cells in the Liver and an Increased Th17/Resting Regulatory T Cell Ratio in Peripheral Blood and in the Liver

Risk Factors for Polyautoimmunity among Patients with Celiac Disease: A Cross-Sectional Survey

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease

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