Ikaros integrates endocrine and immune system development
Shereen Ezzat, Rene Mader, ShunJiang Yu, Terry Ning, Philippe Poussier, Sylvia L. Asa
Shereen Ezzat, Rene Mader, ShunJiang Yu, Terry Ning, Philippe Poussier, Sylvia L. Asa
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Ikaros integrates endocrine and immune system development

Abstract

Ikaros transcription factors are essential regulators of lymphopoiesis and the development of the immune system. We now show that Ikaros is expressed in hormone-producing pituitary corticomelanotroph cells, where it binds the proopiomelanocortin promoter and regulates endogenous gene expression. Loss of Ikaros in vivo results in contraction of the pituitary corticomelanotroph population, reduced circulating adrenocorticotrophic hormone levels, and adrenal glucocorticoid insufficiency. While hemopoietic reconstitution failed to correct this hormonal deficit, the phenotype of reduced body weight and diminished survival was rescued by systemic glucocorticoid-hormone administration. Given the established immunomodulatory properties of glucocorticoid hormones, these findings reveal a novel role for Ikaros in orchestrating immune-endocrine development and function.

Authors

Shereen Ezzat, Rene Mader, ShunJiang Yu, Terry Ning, Philippe Poussier, Sylvia L. Asa

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Figure 1

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Identification of Ikaros and Eos expression in pituitary corticotroph ce...
Identification of Ikaros and Eos expression in pituitary corticotroph cells. (A) Northern blotting of polyA RNA from pituitary corticomelanotroph AtT20 pituitary cells using Ikaros cDNA (top) identifies a doublet transcript of 2.7 and 2.5 kb, consistent with Ik1 and Ik2 mRNA expression. This doublet comigrates with that from pro–B lymphocyte–derived RNA. Eos mRNA expression (middle) is detected at much lower levels in AtT20 cells. The GAPDH loading control is shown immediately below. (B) Western blotting using specific antibodies against Ikaros (left) identifies a 52- and 50-kDa doublet that comigrates with that from lymphocytes. Detection with anti-Eos antibody (right) identifies the predicted 57-kDa product in AtT20 cells. The corresponding β-actin loading controls are shown immediately below. (C) Detection of Ikaros by EMSA of a DNA fragment including the Ikaros consensus binding motif, which binds nuclear extracts (NE) from pituitary corticomelanotroph AtT20 similar to those from pro-B lymphocytes. DNA-protein complexes from pituitary AtT20 cells are competed by 100 M excess of wild-type Ikaros oligonucleotide (Ik oligo) and are supershifted by antibody against Ikaros (arrows) and to a lesser extent by an antibody against Eos.