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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Characterization of Ikaros-type transcription factor-binding elements in...
Characterization of Ikaros-type transcription factor-binding elements in the POMC gene promoter. (A) Potential Ikaros-type binding sites in the POMC –543 promoter were determined with TRANSFAC software. Five potential sites, indicated by A, B, C, D and E, were identified. Other recognized transcription factor–binding elements are indicated. (B) The 5 POMC promoter Ikaros-binding sites were used as EMSA probes with nuclear extracts from AtT20 cells. Note complex formation with fragments A, B, and C but not D and E. Reactions without (–) and with (+) nuclear protein are indicated. (C) Oligonucleotides A, B, and C were further tested in the absence or presence of 100 M excess Ikaros oligonucleotide or a monoclonal antibody against Ikaros (Ik Ab 1), a polyclonal antiserum against Ikaros (Ik Ab 2), Eos (Eos Ab), and a control antibody (Ctrl Ab) against Rb as indicated. As noted in B, the site A complex runs faster than those generated by B or C. The supershifted bands with the antibody against Ikaros are uniformly more intense and migrate slightly higher than those with the antibody against Eos. Increased amounts (μl) of Ikaros antiserum (second panel) result in increased intensity of the supershifted bands.