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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Disrupted corticomelanotroph development in Ikaros-deficient mice impair...
Disrupted corticomelanotroph development in Ikaros-deficient mice impairs pituitary-adrenocortical function. Levels of circulating hormones of the pituitary-adrenal axis including the POMC-derived peptides ACTH (A) and MSH (B) and the ACTH-dependent adrenocortical hormone corticosterone (C) were measured by immunoassay in Ikaros-null (n = 8), heterozygous (n = 31), and wild-type littermates (n = 18) at 3 weeks of age. The reductions in ACTH, MSH, and corticosterone levels were most pronounced in Ikaros-null mice, as illustrated by the horizontal-bar comparisons. (D) Neither lymphocyte reconstitution nor treatment with vehicle changed circulating corticosterone levels in Ikaros-deficient animals. Data are from animals described in Table 1 and reflect the impact of reconstitution with wild-type marrow cells 5 weeks after intrahepatic injection.