NFAT-mediated defects in erythropoiesis cause anemia in Il2−/− mice
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 1992 views | HTML 3037 views | ?
Sabrina Giampaolo1, Gabriela Wójcik2, Stefan Klein-Hessling1,3, Edgar Serfling1,3 and Amiya K. Patra2
1Department of Molecular Pathology, Institute of Pathology, University of Würzburg, 97080 Würzburg, Germany
2Institute of Translational and Stratified Medicine, Peninsula Schools of Medicine and Dentistry, University of Plymouth, Plymouth PL6 8BU, UK
3Comprehensive Cancer Center Mainfranken, University of Würzburg, 97080 Würzburg, Germany
Amiya K. Patra, email: [email protected]
Keywords: erythropoiesis; anemia; IL-2; integrin; cAMP
Received: April 28, 2017 Accepted: November 09, 2017 Published: December 28, 2017
The role of NFAT family transcription factors in erythropoiesis is so far unknown, although their involvement has been suggested previously. We have shown recently that Il2-/- mice develop severe anemia due to defects in KLF1 activity during BM erythropoiesis. Although, KLF1 activity is indispensable for erythropoiesis, the molecular details of Klf1 expression have not yet been elucidated. Here we show that an enhanced NFATc1 activity induced by increased integrin-cAMP signaling plays a critical role in the dysregulation of Klf1 expression and thereby cause anemia in Il2-/- mice. Interestingly, enhanced NFATc1 activity augmented apoptosis of immature erythrocytes in Il2-/- mice. On the other hand, ablation of NFATc1 activity enhanced differentiation of Ter119+ cells in BM. Restoring IL-2 signaling in Il2-/- mice reversed the increase in cAMP-NFAT signaling and facilitated normal erythropoiesis. Altogether, our study identified an NFAT-mediated negative signaling axis, manipulation of which could facilitate erythropoiesis and prevent anemia development.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.