Abstract
BackgroundIL-33 is a pleiotropic cytokine of the IL-1 family, which has been reported to implicate in both innate and adaptive immune responses. Recent studies suggest IL-33 is crucial for regulation of myelopoiesis and myeloid cell activity. Here, we explore the potential effect of IL-33 against hematopoietic injury after total body irradiation (TBI).MethodsC57BL/6 mice were irradiated with a sublethal dose of radiation (600 cGy) and treated with IL-33 at a dose of 3 μg/dose i.p. once a day for seven consecutive days. H&E staining was used to determine the bone marrow cellularity. A flow cytometer was used to quantify the hematopoietic stem cell (HSC) population, cell proliferation, and apoptosis. The colony-forming assay was used to evaluate the clonogenic function of HSCs. RT-qPCR was used to determine the expression of apoptosis-associated genes.ResultsBone marrow HSCs from wild-type mice expressed functional IL-33 receptor (ST2), and treatment with IL-33 promoted the recovery of the HSC pool in vivo and improved the survival of mice after TBI. Conversely, mice with ST2 deficiency showed decreased HSC regeneration and mouse survival after TBI. Of note, IL-33 reduced radiation-induced apoptosis of HSCs and mediated this effect through repression of the p53-PUMA pathway.ConclusionsIL-33 regulates HSC regeneration after myelosuppressive injury through protecting HSCs from apoptosis and enhancing proliferation of the surviving HSCs.
Highlights
IL-33 is a pleiotropic cytokine of the IL-1 family, which has been reported to implicate in both innate and adaptive immune responses
Our results showed that the expression of the IL-33 receptor ST2 on the surface of hematopoietic stem cell (HSC) was rapidly increased in mice when exposed to ionizing radiation
C57BL/C mice were whole-body irradiated with 600 cGy and treated with IL-33 i.p. at a dose of 3 μg/dose/day once a day for 7 consecutive days starting within 1 h after radiation exposure
Summary
IL-33 is a pleiotropic cytokine of the IL-1 family, which has been reported to implicate in both innate and adaptive immune responses. The acute radiation syndrome (ARS) is characterized by a series of complex physiological and morphological developments manifesting eventually in multi-organ failure (MOF) resulting in the death of the casualties [3]. Interleukin-33 is a newly described member of the IL-1 family of cytokines that binds to the IL-33 receptor, formerly known as the orphan receptor ST2 [9, 10]. IL-33 has been reported to be constitutively expressed in the nuclei of endothelial and epithelial cells, and is released into the extracellular space, as an alarmin, after tissue damage to alert the immune system [12].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
