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

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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-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.

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Giampaolo, S., Wójcik, G., Serfling, E., & Patra, A. K. (2017). Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells. Oncotarget, 8(18), 29625–29642. https://doi.org/10.18632/oncotarget.16377

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