Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells
Please always quote using this URN: urn:nbn:de:bvb:20-opus-170947
- 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-γThe 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.…
Author: | Sabrina Giampaolo, Gabriela Wójcik, Edgar Serfling, Amiya K. Patra |
---|---|
URN: | urn:nbn:de:bvb:20-opus-170947 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Pathologisches Institut |
Language: | English |
Parent Title (English): | Oncotarget |
Year of Completion: | 2017 |
Volume: | 8 |
Issue: | 18 |
Pagenumber: | 29625-29642 |
Source: | Oncotarget, 2017, Vol. 8,, No. 18, 29625-29642. DOI: 10.18632/oncotarget.16377 |
DOI: | https://doi.org/10.18632/oncotarget.16377 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28415569 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten |
Tag: | IFN-γ; IL-10; IL-2; hematopoietic stem cells; immune response; immunity; immunology and microbiology section; treg cells |
Release Date: | 2019/10/14 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung |