NFAT-mediated defects in erythropoiesis cause anemia in Il2 -/- mice

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 mice develop severe anemia due to defects in KLF1 activity during BM erythropoiesis. Although, KLF1 activity is indispensable for e...

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Bibliographic Details
Published inOncotarget Vol. 9; no. 11; pp. 9632 - 9644
Main Authors Giampaolo, Sabrina, Wójcik, Gabriela, Klein-Hessling, Stefan, Serfling, Edgar, Patra, Amiya K
Format Journal Article
LanguageEnglish
Published United States Impact Journals LLC 09.02.2018
Subjects
Research Paper
IL-2
erythropoiesis
cAMP
integrin
anemia
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Summary: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 mice develop severe anemia due to defects in KLF1 activity during BM erythropoiesis. Although, KLF1 activity is indispensable for erythropoiesis, the molecular details of 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 expression and thereby cause anemia in mice. Interestingly, enhanced NFATc1 activity augmented apoptosis of immature erythrocytes in mice. On the other hand, ablation of NFATc1 activity enhanced differentiation of Ter119 cells in BM. Restoring IL-2 signaling in 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.
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ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.23745