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About the Authors:
Narendra P. Singh
Contributed equally to this work with: Narendra P. Singh, Udai P. Singh
Affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America
Udai P. Singh
Contributed equally to this work with: Narendra P. Singh, Udai P. Singh
Affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America
Balwan Singh
Affiliation: Primate Research Center, Emory University, Atlanta, Georgia, United States of America
Robert L. Price
Affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America
Mitzi Nagarkatti
Affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America
Prakash S. Nagarkatti
* E-mail: [email protected]
Affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America
Introduction
Aryl hydrocarbon receptor (AhR) is a transcription factor that resides in the cytosol, and is a member of the bHLH-PAS protein family [1], [2]. Activation of AhR leads to conformational change and translocation to the nucleus where it binds to its dimerization partner, aryl hydrocarbon receptor nuclear translocator (ARNT). The AhR-ARNT complex initiates transcription of genes with promoters containing a dioxin-responsive element (DRE) consensus sequence. Wide range chemicals can activate AhR including environmental contaminants such as 2,3,7,8-Tetrachlorodibenzodioxin (TCDD), and other compounds such as tryptophan derivatives, flavonoids and biphenyls [3]. AhR was first discovered and well characterized as a transcription factor responsible for the activation of genes encoding a number of xenobiotic metabolizing enzymes, and mediate the toxicity induced by TCDD [4]. Interestingly, recent studies indicated that AhR activation plays diverse roles in cellular functions, including the regulation of the immune system [5], [6].
Recently, the role of AhR activation in the regulation of T cell differentiation has generated significant interest [7], [8]. AhR was shown to be express by both Th17 and Tregs, and furthermore, AhR activation promoted their differentiation [9], [10]. The development of Tregs and Th17 cells is reciprocally regulated. Thus, while transforming growth factor (TGF)-β1 induces the differentiation of Treg cells [11], the TGF-β1 along with combination of...