Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers

Research output: Contribution to journalArticle

Abstract

Human innate lymphoid cells have been described to exist in different organs, with functional deregulation of these cells contributing to several disease states. Here, we performed the first detailed characterization of the phenotype, tissue-residency properties, and functionality of ILC1s, ILC2s, and ILC3s in the human adult and fetal liver. In addition, we investigated changes in the ILC compartment in liver fibrosis. A unique composition of tissue-resident ILCs was observed in nonfibrotic livers as compared with that in mucosal tissues, with NKp44 ILC3s accounting for the majority of total intrahepatic ILCs. The frequency of ILC2s, representing a small fraction of ILCs in nonfibrotic livers, increased in liver fibrosis and correlated directly with the severity of the disease. Notably, intrahepatic ILC2s secreted the profibrotic cytokine IL-13 when exposed to IL-33 and thymic stromal lymphopoetin (TSLP); these cytokines were produced by hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells in response to TLR-3 stimulation. In summary, the present results provide the first detailed characterization of intrahepatic ILCs in human adult and fetal liver. The results indicate a role for ILC2s in human liver fibrosis, implying that targeting ILC2s might be a novel therapeutic strategy for its treatment.

Details

Authors
  • Marianne Forkel
  • Lena Berglin
  • Eliisa Kekäläinen
  • Adrian Carlsson
  • Emma Svedin
  • Jakob Michaëlsson
  • Maho Nagasawa
  • Jonas S. Erjefält
  • Michiko Mori
  • Malin Flodström-Tullberg
  • Annika Bergquist
  • Hans-Gustaf Ljunggren
  • Magnus Westgren
  • Ulrik Lindforss
  • Danielle Friberg
  • Carl Jorns
  • Ewa Ellis
  • Niklas K Björkström
  • Jenny Mjösberg
Organisations
External organisations
  • Karolinska Institutet
  • Academic Medical Center of University of Amsterdam (AMC)
  • Karolinska University Hospital
  • Linköping University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • Fibrosis, Human, Innate lymphoid cells, Liver, Tissue-residency
Original languageEnglish
Pages (from-to)1280-1294
Number of pages15
JournalEuropean Journal of Immunology
Volume47
Issue number8
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes