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


ABSTRACT: 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.

SUBMITTER: Giampaolo S 

PROVIDER: S-EPMC5839390 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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NFAT-mediated defects in erythropoiesis cause anemia in <i>Il2</i><sup>-/-</sup> mice.

Giampaolo Sabrina S   Wójcik Gabriela G   Klein-Hessling Stefan S   Serfling Edgar E   Patra Amiya K AK  

Oncotarget 20171228 11


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 <i>Il2</i><sup>-/-</sup> mice develop severe anemia due to defects in KLF1 activity during BM erythropoiesis. Although, KLF1 activity is indispensable for erythropoiesis, the molecular details of <i>Klf1</i> expression have not yet been elucidated. Here we show that an enhanced NFATc1 activity induced by increased integrin-cAMP s  ...[more]

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