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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Loss of Ikaros impairs pituitary corticomelanotroph development and ACTH...
Loss of Ikaros impairs pituitary corticomelanotroph development and ACTH expression. (A) The pituitaries of Ikaros-null mice (KO) at E17.5 were compared with age-matched controls from heterozygous (HET) and wild-type littermates as indicated. The sections were taken from the midline of the gland and include the sphenoid bone (S) in the midline below the gland. Note the normal onset and distribution of the corticomelanotroph-specific Tpit factor (upper panels) but reduced ACTH reactivity (lower panels) in heterozygous mice and near complete absence of ACTH in homozygous mice. (B) By 1 week of age, immunocytochemical examination reveals persistent loss of ACTH reactivity in the pituitary of Ikaros-null mice compared with wild-type control littermates. The heterozygous (HET) animals also showed loss of ACTH immunoreactivity, but the glands were larger than those of homozygous animals, and the striking loss involved the intermediate lobe (arrows) that is separated from the anterior lobe by the residual Rathke’s cleft (*) in the mid-portion of the gland. Original magnification, ×63.