Xuexian Yang & Chen Dong
talk with ScienceWatch.com and answer a few
questions about this month's Fast Breaking Paper in the
field of Immunology.
Article Title: T helper 17 lineage differentiation
is programmed by orphan nuclear receptors ROR alpha and ROR
gamma
Authors: Yang,
XXO;Pappu, BP;Nurieva, R;Akimzhanov, A;Kang,
HS;Chung, Y;Ma, L;Shah, B;Panopoulos, AD;Schluns,
KS;Watowich, SS;Tian, Q;Jetten,
AM;Dong,
C
Journal: IMMUNITY
Volume: 28
Issue: 1
Page: 29-39
Year: JAN 2008
* Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol,
1515 Holcombe Blvd, Houston, TX 77030 USA.
(addresses have been truncated)
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.
Coauthor
Chen Dong
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.