Functions Of ZBTB24 In Human T Lymphocytes

Loss-of-function mutations of zbtb24 lead to an autosomal recessive disease ICF2(Immunodeficiency,centromere instability and facial abnormality syndrome type 2,ICF2),with the immunological hallmark of antibody deficiency in circμlations.Although the number of circ ulating memory B cells is greatly reduced or even absent,the numbers of total B or T cells are nomal in most ICF patients.ZBTB24 belongs to the large ZBTB protein family.Many ZBTB family members,including BC L-6,have been shown to play essential roles in the development and/or function of lymphocytes.In line with this,our previous data indicate the ZBTB24 participates in in-vivo antibody productions through regμlating the proliferation and differentiation of human B lymphocytes.Nontheless,given the decreased proliferations of PBMCs isolated from ICF2 patients upon in-vitro stimulations by PHA/anti-CD3,we reasoned that ZBTB24may be involved in T-cell functions as well.Therefore,we used Jurkat cells with high endogenous ZBTB24 expressions as model cells to investigate the functions of ZBTB24in human T cells.We found that knockdown of endogenous ZBTB24 by lentiviral infections significantly inhibits the proliferation of Jurkat cells,which is mainly attributed to the increased cell apoptosis as no effec t on cell-cycle progression was observed.Notably,expressions of the ICF3 gene CDCA7,at both m RNA and protein levels,are greatly reduced in Jurkat cells with downregualted ZBTB24.Knockdown of CDCA7 induces large amounts of Jurkat cells to undergo apoptosis as well.Moreover,cells with reduced expressions of ZBTB24 or CDCA7 display increased sensitivity to TRAIL-induced apoptosis due to upregulated levels of surface death receptor TRAIL-R1.Together,these data indicate that ZBTB24 mod ulates the survival of Jurkat cells through,at least in part,regμlating the expressions of CDCA7.Although detailed molecular mechanisms behind merit further investigations,our res ults presented here demonstrate the involvement of ZBTB24 in T-cell functions.These data indicate that ZBTB24 may modulate in-vivo cellular and humoral responses through CD4~+Th cells,and thus provide another explantation for the immunodeficiency and often-occurred infections observed in ICF2 patients.