Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers
| Autor: | Maho Nagasawa, Jakob Michaëlsson, Jonas S. Erjefält, Adrian Carlsson, Ulrik Lindforss, Danielle Friberg, Niklas K. Björkström, Lena Berglin, Malin Flodström-Tullberg, Marianne Forkel, Eliisa Kekäläinen, Annika Bergquist, Hans-Gustaf Ljunggren, Jenny Mjösberg, Emma Svedin, Michiko Mori, Magnus Westgren, Carl Jorns, Ewa Ellis |
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| Přispěvatelé: | Graduate School, Cell Biology and Histology, Experimental Immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Pathology medicine.medical_specialty Stromal cell Kupffer Cells medicine.medical_treatment Immunology Stimulation Gastroenterology and Hepatology Biology 03 medical and health sciences Fetus Thymic Stromal Lymphopoietin Fibrosis medicine Gastroenterologi Hepatic Stellate Cells Immunology and Allergy Humans Lymphocytes skin and connective tissue diseases Interleukin-13 Natural Cytotoxicity Triggering Receptor 2 Innate lymphoid cell medicine.disease Interleukin-33 Phenotype Immunity Innate Toll-Like Receptor 3 030104 developmental biology Cytokine Liver Hepatic stellate cell Hepatocytes Cytokines |
| Zdroj: | European journal of immunology, 47(8), 1280-1294. Wiley-VCH Verlag |
| ISSN: | 1521-4141 0014-2980 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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