Journal
FRONTIERS IN IMMUNOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.02972
Keywords
JAK; STAT; cytokines; NK cells; ILC; differentiation; kinase inhibitors
Categories
Funding
- Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIG AR041168-12, ZIC AR041169-12, ZIH AR041173-12, ZIC AR041181-11, 1 ZIC AR041207-04]
- NCATS
- NCI
- Italian Association for Cancer Research (AIRC), MFAG 2018 [21311]
- Institut Pasteur (France), Transversal Research Program [PTR-113-17]
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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.
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