The role of protein modifications of T-bet in cytokine production and differentiation of T helper cells

T-bet (t-box protein expressed in t cells,also called as tbx21) was originally cloned as a key transcription factor involved in the commitment of t helper (th) cells to the th1 lineage. t-bet directly activates ifn-γ gene transcription and enhances development of th1 cells. t-bet simultaneously modulates il-2 and th2 cytokines in an ifn-γ-independent manner,resulting in an attenuation of th2 cell development. numerous studies have demonstrated that t-bet plays multiple roles in many subtypes of immune cells,including b cell,dendritic cells,natural killer (nk) cells,nk t cells,and innate lymphoid cells. therefore,t-bet is crucial for the development and coordination of both innate and adaptive immune responses. to fulfill these multiple roles,t-bet undergoes several posttranslational protein modifications,such as phosphorylation at tyrosine,serine,and threonine residues,and ubiquitination at lysine residues,which affect lineage commitment during th cell differentiation. this review presents a current overview of the progress made in understanding the roles of various types of t-bet protein modifications in the regulation of cytokine production during th cell differentiation. © 2014 sera oh and eun sook hwang.