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Journal of Immunology Research
Volume 2014, Article ID 589672, 7 pages
Review Article

The Role of Protein Modifications of T-Bet in Cytokine Production and Differentiation of T Helper Cells

College of Pharmacy, School of Pharmaceutical Sciences and Global Top 5 Research Program, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, C206 Science Building, Seoul 120-750, Republic of Korea

Received 14 March 2014; Accepted 15 April 2014; Published 13 May 2014

Academic Editor: Mizuko Mamura

Copyright © 2014 Sera Oh and Eun Sook Hwang. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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- gene transcription and enhances development of Th1 cells. T-Bet simultaneously modulates IL-2 and Th2 cytokines in an IFN- -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.