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

Forkel, Marianne; Berglin, Lena; Kekäläinen, Eliisa; Carlsson, Adrian; Svedin, Emma; Michaëlsson, Jakob; Nagasawa, Maho; Erjefält, Jonas S. LU ; Mori, Michiko LU and Flodström-Tullberg, Malin, et al. (2017) In European Journal of Immunology 47(8). p.1280-1294
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... (More)

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.

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publication status
published
subject
keywords
Fibrosis, Human, Innate lymphoid cells, Liver, Tissue-residency
in
European Journal of Immunology
volume
47
issue
8
pages
15 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:85022319457
  • wos:000407262000006
ISSN
0014-2980
DOI
10.1002/eji.201646890
language
English
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yes
id
c13f0f85-0b89-4ee8-a824-c79d39ca9618
date added to LUP
2017-08-18 11:41:30
date last changed
2018-03-11 04:42:42
@article{c13f0f85-0b89-4ee8-a824-c79d39ca9618,
  abstract     = {<p>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<sup>−</sup> 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.</p>},
  author       = {Forkel, Marianne and Berglin, Lena and Kekäläinen, Eliisa and Carlsson, Adrian and Svedin, Emma and Michaëlsson, Jakob and Nagasawa, Maho and Erjefält, Jonas S. and Mori, Michiko and Flodström-Tullberg, Malin and Bergquist, Annika and Ljunggren, Hans-Gustaf and Westgren, Magnus and Lindforss, Ulrik and Friberg, Danielle and Jorns, Carl and Ellis, Ewa and Björkström, Niklas K and Mjösberg, Jenny},
  issn         = {0014-2980},
  keyword      = {Fibrosis,Human,Innate lymphoid cells,Liver,Tissue-residency},
  language     = {eng},
  number       = {8},
  pages        = {1280--1294},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers},
  url          = {http://dx.doi.org/10.1002/eji.201646890},
  volume       = {47},
  year         = {2017},
}