A Subset of Liver Resident Natural Killer Cells Is Expanded in Hepatitis C-Infected Patients with Better Liver Function

Details

• Personal Author:
  Aloman C ; Branch AD ; Doyle EH ; El-Shamy A ; Eng F ; Fiel MI ; Florman SS ; Haydel B ; Klepper AL ; Rahman A ; Schiano T
• Description:
  Viral hepatitis leads to immune-mediated liver injury. The rate of disease progression varies between individuals. We aimed to phenotype immune cells associated with preservation of normal liver function during hepatitis C virus (HCV) infection. Clinical data and specimens were obtained from 19 HCV-infected patients undergoing liver transplantation. Liver and peripheral blood mononuclear cells were isolated and eight subsets of innate immune cells were delineated by multiparameter flow cytometry. Cytokine assays and microarrays were performed. Intrahepatic CD56Bright/CD16- natural killer (NK) cells comprised the only subset correlating with better liver function, i.e., lower bilirubin (p = 0.0002) and lower model for end stage of liver disease scores (p = 0.03). The signature of liver NK cells from HCV-infected patients included genes expressed by NK cells in normal liver and by decidual NK cells. Portal vein blood had a higher concentration of interleukin (IL)-10 than peripheral blood (p = 0.03). LMCs were less responsive to toll-like receptor (TLR) stimulation than PBMCs, with fewer pro-inflammatory gene-expression pathways up-regulated after in vitro exposure to lipopolysaccharide and a TLR-7/8 agonist. Hepatic CD56Bright/CD16- NK cells may be critical for maintaining liver homeostasis. Portal vein IL-10 may prime inhibitory pathways, attenuating TLR signaling and reducing responsiveness to pro-inflammatory stimuli. [Description provided by NIOSH]
• Subjects:
  Immune System Occupational Health Safety
• Keywords:
  Cytokines Gene Expression Hepatitis C Immune Reaction Liver Damage Liver Function
• ISSN:
  2045-2322
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; New York ; OSHA Region 2 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  11
• NIOSHTIC Number:
  nn:20068156
• Citation:
  Sci Rep 2021 Jan; 11:1551
• Contact Point Address:
  Andrea D. Branch, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai School, 1425 Madison Ave., Icahn 11-23, New York, NY, 10029, USA
• Email:
  Andrea.Branch@mssm.edu
• Federal Fiscal Year:
  2021
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20170701
• Source Full Name:
  Scientific Reports
• End Date:
  20210630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c1b65b83918353c5dffdcd67d4f62c8a3b60f4cb7b22112c8de2358c1cfc5db33fc2c98509a0390e8bbdee3e507dfac0e73d6a47da3b91abf4e749d353827d99
• Download URL:
  https://stacks.cdc.gov/view/cdc/230369/cdc_230369_DS1.pdf
• File Type:
  [PDF - 4.20 MB ]