Liver type 1 innate lymphoid cells lacking IL-7 receptor are a native killer cell subset fostered by parenchymal niches
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- Asahi, Takuma
- Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University; Graduate School of Medicine, Kyoto University
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- Abe, Shinya
- Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University; Graduate School of Medicine, Kyoto University
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- Cui, Guangwei
- Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University
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- Shimba, Akihiro
- Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University; Department of Human Health Sciences, Graduate School of Medicine, Kyoto University
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- Nabekura, Tsukasa
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba; Department of Immunology, Faculty of Medicine, University of Tsukuba; R&D Center for Innovative Drug Discovery, University of Tsukuba
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- Miyachi, Hitoshi
- Reproductive Engineering Team, Institute for Life and Medical Sciences, Kyoto University
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- Kitano, Satsuki
- Reproductive Engineering Team, Institute for Life and Medical Sciences, Kyoto University
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- Ohira, Keizo
- Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University; Graduate School of Biostudies, Kyoto University
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- Dijkstra, Johannes M
- Center for Medical Science, Fujita Health University
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- Miyazaki, Masaki
- Laboratory of Immunology, Institute for Life and Medical Sciences, Kyoto University
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- Shibuya, Akira
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba; Department of Immunology, Faculty of Medicine, University of Tsukuba; R&D Center for Innovative Drug Discovery, University of Tsukuba
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- Ohno, Hiroshi
- RIKEN Center for Integrative Medical Sciences
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- Ikuta, Koichi
- Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University
Abstract
Group 1 innate lymphoid cells (G1-ILCs), including circulating natural killer (NK) cells and tissue-resident type 1 ILCs (ILC1s), are innate immune sentinels critical for responses against infection and cancer. In contrast to relatively uniform NK cells through the body, diverse ILC1 subsets have been characterized across and within tissues in mice, but their developmental and functional heterogeneity remain unsolved. Here, using multimodal in vivo approaches including fate-mapping and targeting of the interleukin 15 (IL-15)-producing microenvironment, we demonstrate that liver parenchymal niches support the development of a cytotoxic ILC1 subset lacking IL-7 receptor (7 R⁻ ILC1s). During ontogeny, fetal liver (FL) G1-ILCs arise perivascularly and then differentiate into 7 R⁻ ILC1s within sinusoids. Hepatocyte-derived IL-15 supports parenchymal development of FL G1-ILCs to maintain adult pool of 7 R⁻ ILC1s. IL-7R⁺ (7R⁺) ILC1s in the liver, candidate precursors for 7 R⁻ ILC1s, are not essential for 7 R⁻ ILC1 development in physiological conditions. Functionally, 7 R⁻ ILC1s exhibit killing activity at steady state through granzyme B expression, which is underpinned by constitutive mTOR activity, unlike NK cells with exogenous stimulation-dependent cytotoxicity. Our study reveals the unique ontogeny and functions of liver-specific ILC1s, providing a detailed interpretation of ILC1 heterogeneity.
Journal
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- eLife
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eLife 12 2023-06-22
eLife Sciences Publications, Ltd
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Keywords
Details 詳細情報について
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- CRID
- 1050578283037606144
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- ISSN
- 2050084X
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- HANDLE
- 2433/284164
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB