JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis
Janus kinase (JAK) inhibitors are widely used in the treatment of multiple autoimmune and inflammatory diseases. Immunologic and transcriptomic profiling have revealed major alterations on natural killer (NK) cell homeostasis associated with JAK inhibitions, while information on other innate lymphoi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02972/full |
| _version_ | 1818513187497050112 |
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| author | Laura Vian Mimi T. Le Nathalia Gazaniga Jacqueline Kieltyka Christine Liu Giuseppe Pietropaolo Stefania Dell'Orso Stephen R. Brooks Yasuko Furumoto Craig J. Thomas Craig J. Thomas John J. O'Shea Giuseppe Sciumè Massimo Gadina |
| author_facet | Laura Vian Mimi T. Le Nathalia Gazaniga Jacqueline Kieltyka Christine Liu Giuseppe Pietropaolo Stefania Dell'Orso Stephen R. Brooks Yasuko Furumoto Craig J. Thomas Craig J. Thomas John J. O'Shea Giuseppe Sciumè Massimo Gadina |
| author_sort | Laura Vian |
| collection | DOAJ |
| description | Janus kinase (JAK) inhibitors are widely used in the treatment of multiple autoimmune and inflammatory diseases. Immunologic and transcriptomic profiling have revealed major alterations on natural killer (NK) cell homeostasis associated with JAK inhibitions, while information on other innate lymphoid cells (ILCs) is still lacking. Herein, we observed that, in mice, the homeostatic pool of liver ILC1 was less affected by JAK inhibitors compared to the pool of NK cells present in the liver, spleen and bone marrow. JAK inhibition had overlapping effects on the transcriptome of both subsets, mainly affecting genes regulating cell cycle and apoptosis. However, the differential impact of JAK inhibition was linked to the high levels of the antiapoptotic gene Bcl2 expressed by ILC1. Our findings provide mechanistic explanations for the effects of JAK inhibitors on NK cells and ILC1 which could be of major clinically relevance. |
| first_indexed | 2024-12-10T23:57:41Z |
| format | Article |
| id | doaj.art-fa9c74c3391a49eca27412b17c27ed59 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T23:57:41Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fa9c74c3391a49eca27412b17c27ed592022-12-22T01:28:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-12-011010.3389/fimmu.2019.02972489857JAK Inhibition Differentially Affects NK Cell and ILC1 HomeostasisLaura Vian0Mimi T. Le1Nathalia Gazaniga2Jacqueline Kieltyka3Christine Liu4Giuseppe Pietropaolo5Stefania Dell'Orso6Stephen R. Brooks7Yasuko Furumoto8Craig J. Thomas9Craig J. Thomas10John J. O'Shea11Giuseppe Sciumè12Massimo Gadina13Translational Immunology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesTranslational Immunology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesTranslational Immunology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesTranslational Immunology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesTranslational Immunology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, Sapienza University of Rome, Rome, ItalyGenomic Technology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesBiodata Mining and Discovery Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesTranslational Immunology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, United StatesLymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesMolecular Immunology and Inflammation Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, Sapienza University of Rome, Rome, ItalyTranslational Immunology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesJanus kinase (JAK) inhibitors are widely used in the treatment of multiple autoimmune and inflammatory diseases. Immunologic and transcriptomic profiling have revealed major alterations on natural killer (NK) cell homeostasis associated with JAK inhibitions, while information on other innate lymphoid cells (ILCs) is still lacking. Herein, we observed that, in mice, the homeostatic pool of liver ILC1 was less affected by JAK inhibitors compared to the pool of NK cells present in the liver, spleen and bone marrow. JAK inhibition had overlapping effects on the transcriptome of both subsets, mainly affecting genes regulating cell cycle and apoptosis. However, the differential impact of JAK inhibition was linked to the high levels of the antiapoptotic gene Bcl2 expressed by ILC1. Our findings provide mechanistic explanations for the effects of JAK inhibitors on NK cells and ILC1 which could be of major clinically relevance.https://www.frontiersin.org/article/10.3389/fimmu.2019.02972/fullJAK/STATcytokinesNK cellsILCdifferentiationkinase inhibitors |
| spellingShingle | Laura Vian Mimi T. Le Nathalia Gazaniga Jacqueline Kieltyka Christine Liu Giuseppe Pietropaolo Stefania Dell'Orso Stephen R. Brooks Yasuko Furumoto Craig J. Thomas Craig J. Thomas John J. O'Shea Giuseppe Sciumè Massimo Gadina JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis Frontiers in Immunology JAK/STAT cytokines NK cells ILC differentiation kinase inhibitors |
| title | JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis |
| title_full | JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis |
| title_fullStr | JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis |
| title_full_unstemmed | JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis |
| title_short | JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis |
| title_sort | jak inhibition differentially affects nk cell and ilc1 homeostasis |
| topic | JAK/STAT cytokines NK cells ILC differentiation kinase inhibitors |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02972/full |
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