Ikaros integrates endocrine and immune system development.
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.
Ezzat
Shereen
S
Department of Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada.
Mader
Rene
R
Yu
ShunJiang
S
Ning
Terry
T
Poussier
Philippe
P
Asa
Sylvia L
SL
D000324:Adrenocorticotropic Hormone / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004703:Endocrine System / Q000254:growth & development* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D051740:Ikaros Transcription Factor; D007107:Immune System / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; C118760:Zfpn1a4 protein, mouse; D051740:Ikaros Transcription Factor; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone