Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells

• Published in: Oncotarget Vol. 8; no. 18; pp. 29625 - 29642
• Main Authors: Giampaolo, Sabrina, Wójcik, Gabriela, Serfling, Edgar, Patra, Amiya K
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 02.05.2017
• Subjects: Animals; Biomarkers; Cell Self Renewal - genetics; Hematopoiesis - genetics; Hematopoiesis - immunology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Immunophenotyping; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Interleukin-2 - genetics; Interleukin-2 - metabolism; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mice; Mice, Knockout; Research Paper: Immunology; Signal Transduction; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; IFN-γ; Immune response; Immunology and Microbiology Section; Treg cells; IL-2; hematopoietic stem cells; Immunity; IL-10
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.16377

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-Treg cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of Treg activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring Treg population successfully rescued HSC maintenance in Il2-/- mice, preventing IFN-γ activity could do the same even in the absence of Treg 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.