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Thymic Regulation of Autoimmune Disease by Accelerated Differentiation of Foxp3⁺ Regulatory T Cells through IL-7 Signaling Pathway¹

Xi Chen,^2* Lei Fang,^2* Shengli Song, Taylor B. Guo,^* Ailian Liu,^* and Jingwu Z. Zhang^3*

^*Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and Shanghai JiaoTong University School of Medicine, Shanghai, China; and Shanghai Institute of Immunology, Shanghai, China

The exact role of adult thymus in autoimmune disease state is poorly understood. We show here that thymus regulated experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, as evidenced by loss of spontaneous recovery in thymectomized EAE mice. There was progressive enrichment for CD4 single-positive Foxp3⁺ regulatory T cells in thymocytes during the course of EAE and they suppressed the disease when adoptively transferred. Thymus was shown to undergo an active process characterized by accelerated differentiation and proliferation of regulatory T (Treg) cells through a mechanism involving increased expression of IL-7 in stromal cells and dynamic expression of IL-7 receptor in thymic Treg cells. This process preceded EAE recovery and selectively affected Treg over non-Treg cells in the thymus, leading to increased output of thymic Treg cells and self-regulation of EAE. The study reveals a novel role of thymus in self-regulation of autoimmune condition.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Natural Science Foundation of China (NSFC-30430650 and NSFC-30571731), Shanghai Institutes of Biological Sciences (SIBS2008005), and Chinese Academy of Sciences (KSCX1-YW-22).

² X.C. and L.F. contributed equally to this study.

³ Address correspondence and reprint requests to Dr. Jingwu Z. Zhang, Institute of Health Sciences, 225 South Chongqing Road, Shanghai 200025, China. E-mail address: jwzang{at}sibs.ac.cn

⁴ Abbreviations used in this paper: Treg cell, regulatory T cell; EAE, experimental autoimmune encephalomyelitis; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; p.i., postimmunization; SP, single positive; Teff cell, effector T cell; TREC, TCR excision circle; WT, wild type.