The Spatio-Temporal Expression Profiles of CD4 + T Cell Differentiation and Function-Related Genes During EAE Pathogenes
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ORIGINAL ARTICLE
The Spatio-Temporal Expression Profiles of CD4 + T Cell Differentiation and Function-Related Genes During EAE Pathogenesis Yingying Cai,1 Hu Shen,2 Chaoyan Qin,1 Jinfeng Zhou,1 Weiming Lai,1 Juping Pan,2,4 and Changsheng Du1,3,4
Abstract—Multiple sclerosis is a CD4+ T cell-mediated autoimmune disease of the central nervous system. The unbalance of the cytokines and transcription factors critical for CD4+ T cell differentiation and function is probably the main reason that causes MS. We detected the mRNA expression changes of key cytokines and transcription factors which are critical for Th1, Th2, Th17, and Treg cell differentiation and function in different tissues during EAE pathogenesis. We fund that each gene not only has its own featured expression changes, but also has interaction with one another, which composes a network of immunity. Understanding the roles of key cytokines and transcription factors in these processes will help to understand disease pathogenesis and supply indications for disease therapy. KEY WORDS: cytokine; experimental autoimmune encephalomyelitis; multiple sclerosis; transcription factor.
INTRODUCTION Multiple sclerosis (MS) is the most common autoimmune inflammatory disease and is characterized by immunemediated demyelination and neurodegeneration of the cenElectronic supplementary material The online version of this article (doi:10.1007/s10753-016-0469-1) contains supplementary material, which is available to authorized users. 1
Research Center for Translational Medicine at East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, 1239 Si Ping Road, Shanghai, 200092, China 2 Tongji Hospital of Tongji University Branch, Tongji University, 1239 Si Ping Road, Shanghai, 200092, China 3 State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China 4 To whom correspondence should be addressed to Juping Pan at Tongji Hospital of Tongji University Branch, Tongji University, 1239 Si Ping Road, Shanghai, 200092, China. E-mail: [email protected]; and Changsheng Du at Research Center for Translational Medicine at East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, 1239 Si Ping Road, Shanghai, 200092, China. E-mail: [email protected]
tral nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is the widely used animal model that shares many pathological and histological similarities with MS. The pathogenesis of MS/EAE is still unknown, but CD4+ T cell-mediated autoimmunity has long been accepted as one of the most important aspects. The differentiation of CD4+ T cells needs specific transcription factors of each subset. Depending on the cytokine environment, naive CD4+ T cells can differentiate into at least four major subsets—Th1, Th2, Th17, and iTreg cells—and produce pro-inflammatory or anti-inflammatory cytokines [1]. Th1 cells were the
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