Deficiency in interferon type 1 receptor improves definitive erythropoiesis in Klf1 null mice

作者：Manchinu Maria Francesca; Brancia Carla; Caria Cristian Antonio; Musu Ester; Porcu Susanna; Simbula Michela; Asunis Isadora; Perseu Lucia; Ristaldi Maria Serafina^*

来源：Cell Death and Differentiation, 2018, 25(3): 589-599.

DOI：10.1038/s41418-017-0003-5

A key regulatory gene in definitive erythropoiesis is the transcription factor Kruppel-like factor 1 (Klf1). Klf1 null mice die in utero by day 15.5 (E15.5) due to impaired definitive erythropoiesis and severe anemia. Definitive erythropoiesis takes place in erythroblastic islands in mammals. Erythroblastic islands are formed by a central macrophage (Central Macrophage of Erythroblastic Island, CMEI) surrounded by maturating erythroblasts. Interferon-beta (IFN-beta) is activated in the fetal liver's CMEI of Klf1 null mice. The inhibitory effect of IFN-beta on erythropoiesis is known and, therefore, we speculated that IFN-beta could have contributed to the impairment of definitive erythropoiesis in Klf1 knockout (KO) mice fetal liver. To validate this hypothesis, in this work we determined whether the inactivation of type I interferon receptor (Ifnar1) would ameliorate the phenotype of Klf1 KO mice by improving the lethal anemia. Our results show a prolonged survival of Klf1/Ifnar1 double KO embryos, with an improvement of the definitive erythropoiesis and erythroblast enucleation, together with a longer lifespan of CMEI in the fetal liver and also a restoration of the apoptotic program. Our data indicate that the cytotoxic effect of IFN-beta activation in CMEI contribute to the impairment of definitive erythropoiesis associated with Klf1 deprivation.

• 出版日期2018-3