Type 1 Innate Lymphoid Cells Are Critical Pro-Inflammatory Effector Cells in a Fatty Liver Mouse Model of Ischemia-Reperfusion Injury
MedStar Georgetown Transplant Institute, Washington, DC
Meeting: 2022 American Transplant Congress
Abstract number: 190
Keywords: Inflammation, Liver, Mice, knockout, Warm ischemia
Topic: Basic Science » Basic Science » 08 - Innate Immunity; Chemokines, Cytokines, Complement
Session Information
Session Name: Innate Immunity, Chemokines, Cytokines, and Complement
Session Type: Rapid Fire Oral Abstract
Date: Sunday, June 5, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 6:20pm-6:30pm
Location: Hynes Room 309
*Purpose: Innate lymphoid cells (ILCs), the most recently described family of lymphoid cells, play fundamental roles in tissue homeostasis through the production of key cytokine expression. Type 1 ILCs (ILC1) have been implicated in regulating immune-mediated inflammatory diseases, but the role of ILC1s in nonalcoholic fatty liver disease and ischemia-reperfusion injury (IRI) is unclear.
*Methods: B6 wildtype mice were fed either standard chow (control) or a lard-based high fat diet (HFD) for at least 16 weeks. At 24-30 weeks mice were further segmented into an IRI group and a non-IRI group. In the IRI group, mice underwent partial warm IRI for 45 minutes and were sacrificed 24 hours later. Hepatic lymphocytes were isolated and polychromatic flow cytometry (PFC) was used to define ILC1 cells (Lin-NK1.1+ T-bet+Eomos–49a+49b–) and conventional NK cells (cNK) (Lin-NK1.1+ T-bet+Eomes+49a–9b+).
*Results: HFD mice gained significantly more body weight (averaging 50g versus 30g) and liver weight (2.7g versus 1.6g) than controls. The hepatic IRI was confirmed by HE sections and evaluated by Suzuki score system: HFD+IRI mice averaged 2.8 versus 1.9 in control+IRI. Next, we investigated the roles of cNK and ILC1 cells in fatty IRI via PFC. HFD+IRI mice showed a significant increase of ILC1 population and relative decrease of cNK population. Since ILC and cNK cell are a major source of proinflammatory IFN-γ and TNF-α, we measured the level of ex vivo cytokine expression in control+IRI and HFD+IRI. We found that ILC1 in HFD+IRI mice produced significantly more IFN-γ (p=0.01) and TNF-α (p=0.03) compared to control+IRI, indicating that ILC1s are major effector cells in fatty liver IRI. To assess whether ILC1s are key pro-inflammatory effector cells in hepatic IRI, Rag1−/− Tbet−/− double knockout mice that lack T and B cells (Rag1−/−) and Tbet-dependent ILC1 were generated. The Rag1−/− Tbet−/− exhibited absence of the ILC1 population and showed liver protection against IRI as shown by significant decrease of alanine aminotransferase levels.
*Conclusions: Here, we provide a first analysis of ILC1 and cNK in livers of HFD mice following IRI. The population of ILC1 was increased in HFD mice post IRI, which lead to an increased secretion of IFN-γ and TNF-α. Studies in Rag1−/− Tbet−/− mice suggested that Tbet-expressing ILC1s play a key role in IRI. This could pave the way for further studies that seek to reduce fatty liver IRI via targeting ILC1s.
To cite this abstract in AMA style:
Kang J, Liggett J, Oza K, Cui Y, Loh K, Kwon D, Kallakury B, Fishbein T, Cui W, Kahn K, Kroemer A. Type 1 Innate Lymphoid Cells Are Critical Pro-Inflammatory Effector Cells in a Fatty Liver Mouse Model of Ischemia-Reperfusion Injury [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/type-1-innate-lymphoid-cells-are-critical-pro-inflammatory-effector-cells-in-a-fatty-liver-mouse-model-of-ischemia-reperfusion-injury-2/. Accessed September 7, 2024.« Back to 2022 American Transplant Congress