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

Sabrina Giampaolo; Gabriela Wójcik; Edgar Serfling; Amiya K. Patra

doi:10.18632/oncotarget.16377

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Research Papers: Immunology:

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

Sabrina Giampaolo, Gabriela Wójcik, Edgar Serfling and Amiya K. Patra _

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Oncotarget. 2017; 8:29625-29642. https://doi.org/10.18632/oncotarget.16377

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Abstract

Sabrina Giampaolo1, Gabriela Wójcik2, Edgar Serfling1,3 and Amiya K. Patra1,2

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-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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Research Papers: Immunology:

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

Abstract