title: Normocaloric low cholesterol diet modulates Th17/Treg balance in patients with chronic hepatitis C virus infection.
abstract: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02038387.
authors.affiliation: Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy; Institute of Molecular Biology and Pathology, National Research Council, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Maggio
authors.affiliation: Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Viscomi
authors.affiliation: Predictive Medicine Unit, Sapienza University, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Andreozzi
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Ettorre
authors.affiliation: Predictive Medicine Unit, Sapienza University, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Viscogliosi
authors.affiliation: Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Barbaro
authors.affiliation: Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy.
authors.forename: Manuele
authors.initials: M
authors.lastname: Gori
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.affiliation: Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy; Institute of Molecular Biology and Pathology, National Research Council, Rome, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Balsano
mesh_terms: D002452:Cell Count; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004032:Diet; D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000821:virology; D057093:Orphan Nuclear Receptors / Q000235:genetics; D010865:Pilot Projects; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D002791:Cholesterol, Dietary; D020381:Interleukin-17; D007378:Interleukins; D000071518:Liver X Receptors; D055651:NK Cell Lectin-Like Receptor Subfamily B; D057093:Orphan Nuclear Receptors; D000097043:Interleukin-22