Normocaloric Low Cholesterol Diet Modulates Th17/Treg Balance in Patients with Chronic Hepatitis C Virus Infection
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{"title"=>"Normocaloric low cholesterol diet modulates Th17/Treg balance in patients with chronic hepatitis C virus infection", "type"=>"journal", "authors"=>[{"first_name"=>"Roberta", "last_name"=>"Maggio", "scopus_author_id"=>"36884945600"}, {"first_name"=>"Carmela", "last_name"=>"Viscomi", "scopus_author_id"=>"56127002100"}, {"first_name"=>"Paola", "last_name"=>"Andreozzi", "scopus_author_id"=>"6602670981"}, {"first_name"=>"Gabriella", "last_name"=>"D'Ettorre", "scopus_author_id"=>"6701506536"}, {"first_name"=>"Giovanni", "last_name"=>"Viscogliosi", "scopus_author_id"=>"43361839300"}, {"first_name"=>"Barbara", "last_name"=>"Barbaro", "scopus_author_id"=>"7003440283"}, {"first_name"=>"Manuele", "last_name"=>"Gori", "scopus_author_id"=>"56284669400"}, {"first_name"=>"Vincenzo", "last_name"=>"Vullo", "scopus_author_id"=>"7006175556"}, {"first_name"=>"Clara", "last_name"=>"Balsano", "scopus_author_id"=>"55886160400"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84919827783", "doi"=>"10.1371/journal.pone.0112346", "sgr"=>"84919827783", "pmid"=>"25532016", "issn"=>"19326203", "pui"=>"600996481"}, "id"=>"aed6577b-4e99-3915-8bae-961270fb62bc", "abstract"=>"UNLABELLED: Hepatitis C virus (HCV) infection is associated with hepatic and extrahepatic manifestations, including immunological disorders. Chronic Hepatitis C (CHC) is often characterized by cholesterol and lipid metabolism alterations, leading to hepatic steatosis. Cholesterol metabolism, in fact, is crucial for the viral life cycle. Recent works described that a higher dietary cholesterol intake is associated with the progression of HCV-related liver disease. CHC patients have increased levels of T helper 17 (Th17)-cells, a lymphocytic population involved in the pathogenesis of liver inflammation and autoimmune hepatitis. The balance between Th17 and regulatory T (Treg) cells is crucial for chronic inflammation and autoimmunity. Th17-cell differentiation is deeply influenced by the activation LXRs, nuclear receptors modulating cholesterol homeostasis. Moreover, HCV may affect these nuclear receptors, and cholesterol metabolism, through both direct and indirect mechanisms. On these bases, we hypothesized that modulation of cholesterol levels through Normocaloric Low Cholesterol Diet (NLCD) may represent an innovative strategy to reduce the progression of HCV infection, through the modulation of peripheral Th17/Treg balance. To this end, we performed a pilot study to investigate whether a Normocaloric Low Cholesterol Diet may be able to modulate Th17/Treg balance in patients affected by chronic HCV infection. After 30 days of NLCD CHC patients showed a significant reduction in Th17 cells frequency, which correlated with strong reduction of IL-17 and IL-22 serum levels. At the same time, we appreciated an increase in the percentage of Treg cells, thus improving Treg/Th17 balance. Moreover, we observed an increased expression of LXRs and their target genes: SREBP-1c and ABCA-1. In conclusion, NLCD finely regulates Th17/Treg balance, improving immune system response in CHC patients. This study could pave the way for new treatments of CHC patients, suggesting that change in lifestyle could support the management of these patients, promoting well-being and possibly hindering disease progression.\\n\\nTRIAL REGISTRATION: ClinicalTrials.gov NCT02038387.", "link"=>"http://www.mendeley.com/research/normocaloric-low-cholesterol-diet-modulates-th17treg-balance-patients-chronic-hepatitis-c-virus-infe-1", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>11, "Agricultural and Biological Sciences"=>3, "Psychology"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Psychology"=>{"Psychology"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1852564"], "description"=>"<p>CONSORT Flow Diagram.</p>", "links"=>[], "tags"=>["lipid metabolism alterations", "CHC patients", "Chronic Hepatitis C Virus Infection Hepatitis C virus", "lxr", "T helper 17", "treg", "abca", "HCV infection", "Chronic hepatitis C", "NLCD CHC patients", "srebp", "receptors modulating cholesterol homeostasis", "Normocaloric Low Cholesterol Diet", "il", "nct", "Th 17 cells frequency"], "article_id"=>1277339, "categories"=>["Biological Sciences"], "users"=>["Roberta Maggio", "Carmela Viscomi", "Paola Andreozzi", "Gabriella d'Ettorre", "Giovanni Viscogliosi", "Barbara Barbaro", "Manuele Gori", "Vincenzo Vullo", "Clara Balsano"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112346.g001", "stats"=>{"downloads"=>11, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CONSORT_Flow_Diagram_/1277339", "title"=>"CONSORT Flow Diagram.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-22 02:57:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1852582", "https://ndownloader.figshare.com/files/1852583"], "description"=>"<div><p></p><p>Hepatitis C virus (HCV) infection is associated with hepatic and extrahepatic manifestations, including immunological disorders. Chronic Hepatitis C (CHC) is often characterized by cholesterol and lipid metabolism alterations, leading to hepatic steatosis. Cholesterol metabolism, in fact, is crucial for the viral life cycle. Recent works described that a higher dietary cholesterol intake is associated with the progression of HCV-related liver disease. CHC patients have increased levels of T helper 17 (Th17)-cells, a lymphocytic population involved in the pathogenesis of liver inflammation and autoimmune hepatitis. The balance between Th17 and regulatory T (Treg) cells is crucial for chronic inflammation and autoimmunity. Th17-cell differentiation is deeply influenced by the activation LXRs, nuclear receptors modulating cholesterol homeostasis. Moreover, HCV may affect these nuclear receptors, and cholesterol metabolism, through both direct and indirect mechanisms. On these bases, we hypothesized that modulation of cholesterol levels through Normocaloric Low Cholesterol Diet (NLCD) may represent an innovative strategy to reduce the progression of HCV infection, through the modulation of peripheral Th17/Treg balance. To this end, we performed a pilot study to investigate whether a Normocaloric Low Cholesterol Diet may be able to modulate Th17/Treg balance in patients affected by chronic HCV infection. After 30 days of NLCD CHC patients showed a significant reduction in Th17 cells frequency, which correlated with strong reduction of IL-17 and IL-22 serum levels. At the same time, we appreciated an increase in the percentage of Treg cells, thus improving Treg/Th17balance. Moreover, we observed an increased expression of LXRs and their target genes: SREBP-1c and ABCA-1. In conclusion, NLCD finely regulates Th17/Treg balance, improving immune system response in CHC patients. This study could pave the way for new treatments of CHC patients, suggesting that change in lifestyle could support the management of these patients, promoting well-being and possibly hindering disease progression.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href=\"http://clinicaltrials.gov/ct2/show/NCT02038387\" target=\"_blank\">NCT02038387</a></p></div>", "links"=>[], "tags"=>["lipid metabolism alterations", "CHC patients", "Chronic Hepatitis C Virus Infection Hepatitis C virus", "lxr", "T helper 17", "treg", "abca", "HCV infection", "Chronic hepatitis C", "NLCD CHC patients", "srebp", "receptors modulating cholesterol homeostasis", "Normocaloric Low Cholesterol Diet", "il", "nct", "Th 17 cells frequency"], "article_id"=>1277353, "categories"=>["Biological Sciences"], "users"=>["Roberta Maggio", "Carmela Viscomi", "Paola Andreozzi", "Gabriella d'Ettorre", "Giovanni Viscogliosi", "Barbara Barbaro", "Manuele Gori", "Vincenzo Vullo", "Clara Balsano"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0112346.s001", "https://dx.doi.org/10.1371/journal.pone.0112346.s002"], "stats"=>{"downloads"=>4, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Normocaloric_Low_Cholesterol_Diet_Modulates_Th17_Treg_Balance_in_Patients_with_Chronic_Hepatitis_C_Virus_Infection_/1277353", "title"=>"Normocaloric Low Cholesterol Diet Modulates Th17/Treg Balance in Patients with Chronic Hepatitis C Virus Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-12-22 02:57:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1852580"], "description"=>"<p>T0 =  Before NLCD; T30 =  After NLCD; Pts =  Patients; F = Females; M = Males; BMI =  Body max index; HOMA-IR = Homeostatic model assessment-insulin resistance; HDL =  High-density lipoprotein; LDL = Low density lipoprotein; ALT = Alanine transaminase; AST = Aspartate transaminase; GGT = Gamma-glutamyl transferase; AP = Alkaline phosphatase; hsCRP = high-sensitivity C-reactive Protein. Statistical significance was accepted at <i>p</i><0.05; NS = Not significant. Values are presented as mean± SD.</p><p>Clinical and biochemical characteristics of studied patients before and after NLCD.</p>", "links"=>[], "tags"=>["lipid metabolism alterations", "CHC patients", "Chronic Hepatitis C Virus Infection Hepatitis C virus", "lxr", "T helper 17", "treg", "abca", "HCV infection", "Chronic hepatitis C", "NLCD CHC patients", "srebp", "receptors modulating cholesterol homeostasis", "Normocaloric Low Cholesterol Diet", "il", "nct", "Th 17 cells frequency"], "article_id"=>1277351, "categories"=>["Biological Sciences"], "users"=>["Roberta Maggio", "Carmela Viscomi", "Paola Andreozzi", "Gabriella d'Ettorre", "Giovanni Viscogliosi", "Barbara Barbaro", "Manuele Gori", "Vincenzo Vullo", "Clara Balsano"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112346.t001", "stats"=>{"downloads"=>4, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_and_biochemical_characteristics_of_studied_patients_before_and_after_NLCD_/1277351", "title"=>"Clinical and biochemical characteristics of studied patients before and after NLCD.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-22 02:57:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1852579"], "description"=>"<p>Serum levels of pro-inflammatory cytokines were lowered by NLCD in CHC and NAFLD/NASH patients. Data are expressed as mean ±SD; all samples were assessed in triplicate. Error bars illustrate SD. *<i>P</i><0.05; **<i>P</i><0.01.</p>", "links"=>[], "tags"=>["lipid metabolism alterations", "CHC patients", "Chronic Hepatitis C Virus Infection Hepatitis C virus", "lxr", "T helper 17", "treg", "abca", "HCV infection", "Chronic hepatitis C", "NLCD CHC patients", "srebp", "receptors modulating cholesterol homeostasis", "Normocaloric Low Cholesterol Diet", "il", "nct", "Th 17 cells frequency"], "article_id"=>1277350, "categories"=>["Biological Sciences"], "users"=>["Roberta Maggio", "Carmela Viscomi", "Paola Andreozzi", "Gabriella d'Ettorre", "Giovanni Viscogliosi", "Barbara Barbaro", "Manuele Gori", "Vincenzo Vullo", "Clara Balsano"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112346.g005", "stats"=>{"downloads"=>0, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_levels_of_A_TGF_946_HA_and_B_IL_23_obtained_from_NAFLD_NASH_and_CHC_patients_before_and_after_NLCD_/1277350", "title"=>"Serum levels of (A) TGF-β, HA and (B) IL-23 obtained from NAFLD/NASH and CHC patients before and after NLCD.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-22 02:57:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1852571"], "description"=>"<p>Evaluation of Treg cells by flow cytometry was determined as percentage of CD127low/-CD25+FoxP3+ cells within the CD3+CD4+compartment. We reported the dot plots of representative experiments, with the percentage of CD25+CD4+ Treg cells, which CD25+ are CD127 low or negative, and the percentage of CD4+CD25+CD127low/-FOXP3+ Treg cells before and after NLCD in peripheral blood of CHC (A) and NAFLD/NASH patients (B). In table, we reported a statistically significant difference between T0 and T30 in Treg-cell frequency in CHC, but not in NAFLD/NASH patients. In C) We represents the changes in ratio between CD4+CD25+CD127low/-FOXP3+ Treg and Th17 (IL-17<sup>+</sup>CD161<sup>+</sup>CD4<sup>+</sup> T) cells frequencies obtained from both groups studied before and after NLCD. Horizontal bars represent the median values of indicated index. *<i>P</i><0.05; **<i>P</i><0.01.</p>", "links"=>[], "tags"=>["lipid metabolism alterations", "CHC patients", "Chronic Hepatitis C Virus Infection Hepatitis C virus", "lxr", "T helper 17", "treg", "abca", "HCV infection", "Chronic hepatitis C", "NLCD CHC patients", "srebp", "receptors modulating cholesterol homeostasis", "Normocaloric Low Cholesterol Diet", "il", "nct", "Th 17 cells frequency"], "article_id"=>1277346, "categories"=>["Biological Sciences"], "users"=>["Roberta Maggio", "Carmela Viscomi", "Paola Andreozzi", "Gabriella d'Ettorre", "Giovanni Viscogliosi", "Barbara Barbaro", "Manuele Gori", "Vincenzo Vullo", "Clara Balsano"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112346.g003", "stats"=>{"downloads"=>1, "page_views"=>139, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Change_of_the_Treg_cell_frequency_and_Treg_Th17_ratio_in_NAFLD_NASH_and_CHC_patients_before_and_after_NLCD_/1277346", "title"=>"Change of the Treg-cell frequency and Treg/Th17 ratio in NAFLD/NASH and CHC patients, before and after NLCD.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-22 02:57:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1852575"], "description"=>"<p>In CHC patients, after NLCD, we observed highly significant changes in LXRα, LXRβ and ABCA-1 mRNA levels, respect to before NLCD (A). No significant changes were observed in NAFLD/NASH patients after NLCD (B). Data are expressed as mean ±SD; all samples were assessed in triplicate. Error bars illustrate SD. *<i>P</i><0.05; **<i>P</i><0.01.</p>", "links"=>[], "tags"=>["lipid metabolism alterations", "CHC patients", "Chronic Hepatitis C Virus Infection Hepatitis C virus", "lxr", "T helper 17", "treg", "abca", "HCV infection", "Chronic hepatitis C", "NLCD CHC patients", "srebp", "receptors modulating cholesterol homeostasis", "Normocaloric Low Cholesterol Diet", "il", "nct", "Th 17 cells frequency"], "article_id"=>1277348, "categories"=>["Biological Sciences"], "users"=>["Roberta Maggio", "Carmela Viscomi", "Paola Andreozzi", "Gabriella d'Ettorre", "Giovanni Viscogliosi", "Barbara Barbaro", "Manuele Gori", "Vincenzo Vullo", "Clara Balsano"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112346.g004", "stats"=>{"downloads"=>3, "page_views"=>42, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_mRNA_expression_of_LXRs_and_related_gene_obtained_from_PBMCs_of_NAFLD_NASH_and_CHC_patients_after_NLCD_/1277348", "title"=>"Relative mRNA expression of LXRs and related-gene obtained from PBMCs of NAFLD/NASH and CHC patients, after NLCD.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-22 02:57:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1852568"], "description"=>"<p>A) Before (T0) and after (T30) NLCD, in CHC patients, we observed a statistically significant decrease of IL-17- and IL-22-producing cells among the indicated CD161<sup>+</sup>CD4<sup>+</sup>T fractions and gated live CD4<sup>+</sup>CD3<sup>+</sup> lymphocytes. B) These changes in frequency of IL-17<sup>+</sup> and IL-22<sup>+</sup>Th17 cells did not reach statistical significance before (T0) and after (T30) NLCD in NAFLD/NASH patients. C) After diet in CHC and NAFLD/NASH patients, we observed the same trend of serum levels of IL-17 and IL-22, even if no statistical significance was reached in NAFLD/NASH patients. One representative plot of all independent experiments is shown. *<i>P</i><0.05; **<i>P</i><0.01; ***<i>P</i><0.001.</p>", "links"=>[], "tags"=>["lipid metabolism alterations", "CHC patients", "Chronic Hepatitis C Virus Infection Hepatitis C virus", "lxr", "T helper 17", "treg", "abca", "HCV infection", "Chronic hepatitis C", "NLCD CHC patients", "srebp", "receptors modulating cholesterol homeostasis", "Normocaloric Low Cholesterol Diet", "il", "nct", "Th 17 cells frequency"], "article_id"=>1277343, "categories"=>["Biological Sciences"], "users"=>["Roberta Maggio", "Carmela Viscomi", "Paola Andreozzi", "Gabriella d'Ettorre", "Giovanni Viscogliosi", "Barbara Barbaro", "Manuele Gori", "Vincenzo Vullo", "Clara Balsano"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112346.g002", "stats"=>{"downloads"=>1, "page_views"=>54, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_17_and_IL_22_CD161_CD4_T_cellphenotype_in_CHC_and_NAFLD_NASH_patients_before_and_after_NLCD_/1277343", "title"=>"IL-17<sup>+</sup>and IL-22<sup>+</sup>CD161<sup>+</sup>CD4<sup>+</sup>T-cellphenotype in CHC and NAFLD/NASH patients before and after NLCD.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-22 02:57:00"}

PMC Usage Stats | Further Information

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Relative Metric

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