Ikaros integrates endocrine and immune system development
Shereen Ezzat, … , Philippe Poussier, Sylvia L. Asa
Shereen Ezzat, … , Philippe Poussier, Sylvia L. Asa
Published April 1, 2005
Citation Information: J Clin Invest. 2005;115(4):1021-1029. https://doi.org/10.1172/JCI22486.
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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 pituitary-adrenocortical function in Ikaros-deficient mice con...
Disrupted pituitary-adrenocortical function in Ikaros-deficient mice contributes to impaired growth and diminished survival. (A) Health status and weight were recorded daily. Compared with Ikaros heterozygous and wild-type control littermates, Ikaros-null mice exhibit growth retardation from birth. Treatment with glucocorticoid hormone (+) compared with vehicle alone resulted in significant weight increase in Ikaros-null mice, an effect not as evident in heterozygous animals. No significant impact of glucocorticoid treatment was observed in wild-type control littermates. Values shown represent the mean weights in grams and, where statistically significant (P < 0.02), treatment effects are denoted by an asterisk. (B) Kaplan-Meier curve depicting the diminished survival of homozygous Ikaros-deficient mice treated with vehicle alone (dashed line; n = 8). The increased mortality was reversed with complete survival in hormone-treated Ikaros-null mice beyond 6 weeks as indicated by the solid line (n = 7). #P < 0.05.