Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells
Year: 2017
Type: article
Abstract: // Sabrina Giampaolo 1 , Gabriela Wójcik 2 , Edgar Serfling 1,3 and Amiya K. Patra 1,2 1 Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Würzburg, Germany 2 Institute of Translational and Stratified Medicine, Peninsula Schools of Medicine and Dentistry, University of Plymouth, Plymouth, UK 3 Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany Correspondence to: Amiya K. Patra, email: // Keywords : hematopoietic stem cells, IL-2, Treg cells, IL-10, IFN-γ, Immunology and Microbiology Section, Immune response, Immunity Received : November 17, 2016 Accepted : March 06, 2017 Published : March 18, 2017 Abstract The role of IL-2 in HSC maintenance is unknown. Here we show that Il2 -/- mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2 -/- mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2 -/- mice shows that the IL-2-T reg cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of T reg activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring T reg population successfully rescued HSC maintenance in Il2 -/- mice, preventing IFN-γ activity could do the same even in the absence of T reg cells. Our study suggests that equilibrium in IL-2 and IFN-γ activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-γ treatment might help to restore hematopoiesis.
Source: Oncotarget
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Awards: G3863769718, G6379834337, G6678805632
OpenAlex ID: W2595859136