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Thymus Exosomes-Like Particles Induce Regulatory T Cells¹

Gui-Jun Wang^*,, Yuelong Liu^*,, Aijian Qin, Spandan V. Shah^*, Zhong-bin Deng^*, Xiaoyu Xiang^*, Ziqiang Cheng^*, Cunren Liu^*, Jianhua Wang^*, Liming Zhang^*, William E. Grizzle and Huang-Ge Zhang^2,*,

^* Division of Clinical Immunology and Rheumatology, Department of Medicine, and Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294; Birmingham Veterans Administration Medical Center, Birmingham, AL 35233; and College of Veterinary Medicine, Yangzhou University, Yangzhou, China

Exosomes released from different types of cells have been proposed to contribute to intercellular communication. We report that thymic exosome-like particles (ELPs) released from cells of the thymus can induce the development of Foxp3⁺ regulatory T (Treg) cells in the lung and liver. Thymic ELPs also induce the conversion of thymic CD4⁺CD25^– T cells into Tregs. Tregs induced by thymic ELPs suppress the proliferation of CD4⁺CD25^– T cells in vitro and in vivo. We further show that neutralization of TGF-β in ELPs partially reverses thymic ELP-mediated induction of CD4⁺Foxp3⁺ T cells in the lung and liver. This study demonstrates that thymic ELPs participate in the induction of Foxp3⁺ Tregs. Also, TGF-β of thymic ELPs might be required for the generation of Tregs in the peripheral tissues.

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 National Institutes of Health Grants R01CA116092, R01CA107181, and R01AT004294; Birmingham Veterans Administration Medical Center Merit Review Grants (H.-G.Z.); and grants from Susan G. Komen Breast Cancer Foundation.

² Address correspondence and reprint requests to Dr. Huang-Ge Zhang, University of Alabama at Birmingham, SIBR306, 1825 University Boulevard, Birmingham, AL 35294-0007. E-mail address: Huang-Ge.Zhang{at}ccc.uab.edu

³ Abbreviations used in this paper: MVB, multivesicular body; ELP, thymes exosome-like particle; Treg, regulatory T cell; AC, accessory cell; Teff, T effector cell.

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