期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 149, 期 5, 页码 1772-1785出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2021.10.012
关键词
ILC; NK cells; glucocorticoids; hematopoietic stem cell; HSCT
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [21147, 19920]
- RC-2020 OPBG
- European Union's Horizon 2020 Research and Innovation Programme under the Marie Sk1odowska-Curie grant [800924]
This study investigates the effect of glucocorticoids (GCs) on the development of innate lymphoid cells (ILCs). The results demonstrate that GCs impair lymphoid development while promoting the differentiation of NK cells. Additionally, recipients of hematopoietic stem cell transplantation treated with GCs show a significant reduction in circulating hILCs.
Background: Innate lymphoid cells (ILCs) comprise cytotoxic natural killer (NK) cells and helper ILCs (hILCs). Human hILC development is less characterized as compared with that of NK cells, although all ILCs are developmentally related. It has been reported that the immunosuppressive drugs glucocorticoids (GCs) regulate ILC function, but whether they control ILC differentiation from hematopoietic stem cells (HSCs) is unknown. Objectives: This study sought to analyze the effect of GCs on ILC development from HSCs. Methods: This study exploited an in vitro system to generate and expand from peripheral blood HSCs a multipotent CD56(+) ILC precursor able to differentiate into NK cells, ILC1s, and ILC3s. We also analyzed ex vivo, at different time points, the peripheral blood of recipients of allogeneic HSC transplantation who were or were not treated with GCs and compared ILC subset reconstitution. Results: In vitro, GCs favor the generation of NK cells from myeloid precursors, while they strongly impair lymphoid development. In support of these data, recipients of HSC transplantation who had been treated with GCs display a lower number of circulating hILCs, including the ILC precursor (ILCP) previously identified as a systemic substrate for tissue ILC differentiation. Conclusions: GCs impair the development of the CD117(+) ILCP from CD34(+) HSCs, while they do not affect the further steps of ILCP differentiation toward NK cells and hILC subsets. This reflects an association of GC treatment with a marked reduction of circulating hILCs in the recipients of HSC transplantation.
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