Composition and functionality of the intrahepatic innate lymphoid cell‐compartment in human nonfibrotic and fibrotic livers |
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| 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 |
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| Affiliation: | 1. Center for Infectious Medicine, Department of Medicine, Karolinska Institute Stockholm, Sweden;2. Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands;3. Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, Lund, Sweden;4. Department of Molecular Medicine and Surgery, Karolinska Institute and Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden;5. Center for Fetal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden;6. Department of Otorhinolaryngology, CLINTEC, KI, Stockholm, Sweden;7. Division of Transplantation Surgery, CLINTEC, Karolinska Institutet (KI), Stockholm, Sweden;8. Department of Clinical and Experimental Medicine, Link?ping University, Sweden |
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| 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. |
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| Keywords: | Innate lymphoid cells Liver Fibrosis Human Tissue‐residency |
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