Liver type 1 innate lymphoid cells lacking IL-7 receptor are a native killer cell subset fostered by parenchymal niches
- Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Japan
- Graduate School of Medicine, Kyoto University, Japan
- Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Japan
- Department of Immunology, Faculty of Medicine, University of Tsukuba, Japan
- R&D Center for Innovative Drug Discovery, University of Tsukuba, Japan
- Reproductive Engineering Team, Institute for Life and Medical Sciences, Kyoto University, Japan
- Graduate School of Biostudies, Kyoto University, Japan
- Center for Medical Science, Fujita Health University, Japan
- Laboratory of Immunology, Institute for Life and Medical Sciences, Kyoto University, Japan
- RIKEN Center for Integrative Medical Sciences, Japan
Figures
Figure 1 with 1 supplement
Fetal and adult liver contain bona fide ILC1s lacking IL-7R.
(A) Gating strategy of subpopulations of G1-ILCs (CD3−NK1.1+NKp46+) in the E18.5 fetal liver (FL), adult liver (AL), and bone marrow (BM). iILC1, immature ILC1. Data represent three independent …
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Figure 1—source data 1
Fetal and adult liver contain bona fide ILC1s lacking IL-7R.
- https://cdn.elifesciences.org/articles/84209/elife-84209-fig1-data1-v1.xlsx
Figure 1—figure supplement 1
Characterization of fetal and adult G1-ILC identities.
(A and B) Flow cytometry (FCM) analysis of AL lymphocytes in control or Il7−/− mice. Representative FCM profiles of G1-ILCs (A) and the cell number of each cell population (B) are shown. Data …
Figure 2 with 1 supplement
7R+ ILC1 s are dispensable for the development of 7 R− ILC1s in AL.
(A–C) Kinetics of IL-7Rα expression on liver non-NK G1-ILCs with age. Representative FCM profiles (A), the percentages within G1-ILCs (B), and the cell number (C) are shown. Data represent or are …
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Figure 2—source data 1
7R+ ILC1s are dispensable for the development of 7 R− ILC1s in AL.
- https://cdn.elifesciences.org/articles/84209/elife-84209-fig2-data1-v1.xlsx
Figure 2—figure supplement 1
BM iILC1s have ability to give rise to AL 7R+ ILC1 s in vivo.
(A) Representative FCM profiles and adjunct histograms of IL-7R and IL-18R1 expressions on transferred AL 7 R− (blue) and 7R+ (orange) ILC1s detected in the host liver at 4 weeks post-transfer. Data …
Figure 3 with 1 supplement
FL G1-ILCs exclusively give rise to 7 R− ILC1s.
(A and B) FCM analysis of transferred FL G1-ILCs (CD45.1) detected in the host liver (CD45.2) at 4 weeks post-transfer. Representative FCM profiles (A) and the percentages of transferred cell fate (B…
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Figure 3—source data 1
FL G1-ILCs exclusively give rise to 7 R− ILC1s.
- https://cdn.elifesciences.org/articles/84209/elife-84209-fig3-data1-v1.xlsx
Figure 3—figure supplement 1
FL G1-ILCs contribute to AL 7 R− ILC1 pool.
(A) FCM analysis of tdTomato+ cells in AL of Ncr1-CreERT2 Rosa26-tdTomato mice treated with tamoxifen at E17.5. Representative FCM plots in neonates and 4 weeks old mice are shown. Data represent …
Figure 4
Liver G1-ILCs shift distributions from parenchyma to sinusoids during development.
(A and B) 3D-reconstructed immunofluorescence images of frozen sections of FL from WT mice (A; n=4) and AL from Cxcr6GFP/+ mice (B; n=4) stained with anti-NKp46 (magenta) and anti-CD31 and/or …
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Figure 4—source data 1
Liver G1-ILCs shift distributions from parenchyma to sinusoids during development.
- https://cdn.elifesciences.org/articles/84209/elife-84209-fig4-data1-v1.xlsx
Figure 5 with 1 supplement
Hepatocytes provide the parenchymal IL-15 niche regulating the local development of 7 R− ILC1s.
(A and B) Single nuclei RNA-seq (snRNA-seq) analysis of mouse whole liver cells (Liver Cell Atlas; https://www.livercellatlas.org/). UMAP visualization (A) and expression levels of Il15 and Il15ra (B…
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Figure 5—source data 1
Hepatocytes provide the parenchymal IL-15 niche regulating the local development of 7 R− ILC1s.
- https://cdn.elifesciences.org/articles/84209/elife-84209-fig5-data1-v1.xlsx
Figure 5—figure supplement 1
Liver IL-15-producing cells supports lymphoid cells in a subset-dependent manner.
(A) Expression of GFP on AL NK cells, 7 R− ILC1s, and 7R+ ILC1s in Cxcr6GFP/+ mice. Data represent two independent experiments (n=4 for all subsets). (B) UMAP visualization of snRNA-seq analysis of …
Figure 6 with 1 supplement
7 R− ILC1s exhibit cytotoxicity via granzyme B expression underpinned by steady-state mTOR activation.
(A and B) Granzyme B expression on each AL G1-ILC population in control or IL-15/IL-15Rα-treated mice. Representative histograms (A), MFI (B, left), and its fold change after the IL-15/IL-15Rα …
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Figure 6—source data 1
7 R− ILC1s exhibit cytotoxicity via granzyme B expression underpinned by steady-state mTOR activation.
- https://cdn.elifesciences.org/articles/84209/elife-84209-fig6-data1-v1.xlsx
Figure 6—figure supplement 1
Differential effector molecule expression and cytokine responsiveness among heterogenous G1-ILC subsets.
(A and B) Expression of FasL (A) (two independent experiments; n=6 for PBS and IL-15/IL-15Rα) and TRAIL (B) (two independent experiments; n=6 for PBS and IL-15/IL-15Rα) on each AL G1-ILC population …
Author response image 1
