Why do you think your paper is highly cited?

Th17, as a newly defined T helper lineage, regulates tissue inflammation in host defenses against infections and in autoimmune diseases through producing cytokines IL-17, IL-17F, IL-21, and IL-22.

In this article, we demonstrated that, in addition to retinoid acid receptor-related orphan nuclear receptor (ROR) (Ivanov et al., Cell, 2006), Th17 cells co-expressed ROR that can drive Th17 differentiation independent of ROR.

ROR and ROR play a synergistic and, to some degree, redundant function in Th17 differentiation. Thus, this study has advanced our understanding on the transcriptional regulation of Th17 cell differentiation and function.

Does it describe a new discovery, methodology, or synthesis of knowledge?

Yes, it describes a new discovery on the transcriptional control of inflammatory, Th17 cell differentiation.

Would you summarize the significance of your paper in layman's terms?

This paper describes two orphan nuclear receptors in programming a subset of T cells that are specialized in promoting inflammatory responses. We showed that compound mutation of both factors led to complete resistance against an autoimmune disease model.

How did you become involved in this research, and were there any problems along the way?

This research is a subsequent episode in a series of studies after we and others defined the novel T helper lineage, Th17. When we performed a microarray study to find that both ROR and ROR genes to be selectively expressed in Th17 cells, we did not have many tools to study them. Luckily, we collaborated with Dr. Anton Jetten at the National Institute of Environmental Health Sciences (NIEHS) who is an expert in the field.

Where do you see your research leading in the future?

Although we know some of the players in Th17 differentiation, we do not know much about mechanistically how they work. In addition, we wish to dissect the stability and plasticity of Th17 cell genetic programs.

Do you foresee any social or political implications for your research?

Yes. Our study may provide useful information in the development of novel treatments for inflammatory diseases that are shown to be caused by Th17 cells.

Xuexian O. Yang, Ph.D.
Instructor
Department of Immunology
MD Anderson Cancer Center
Houston, TX, USA

Chen Dong, Ph.D.
Associate Professor
Department of Immunology
MD Anderson Cancer Center
Houston, TX, USA

Keywords: T helper lineage, autoimmune diseases, retinoid acid receptor-related orphan nuclear receptor, two orphan nuclear receptors, inflammatory diseases.