Thyrocyte-derived exosome-targeted dendritic cells stimulate strong CD4+ T lymphocyte responses

Xuejiao Cui; Shuo Wang; Na Zhao; Shiwei Wang; Zhenzhen Wang; Mingshi Huang; Yongping Liu; Jing Qin; Zhongyan Shan; Weiping Teng; Yushu Li

doi:10.1016/j.mce.2020.110756

Thyrocyte-derived exosome-targeted dendritic cells stimulate strong CD4⁺ T lymphocyte responses

Mol Cell Endocrinol. 2020 Apr 15:506:110756. doi: 10.1016/j.mce.2020.110756. Epub 2020 Feb 8.

Authors

Xuejiao Cui¹, Shuo Wang², Na Zhao³, Shiwei Wang⁴, Zhenzhen Wang⁵, Mingshi Huang⁶, Yongping Liu⁷, Jing Qin⁸, Zhongyan Shan⁹, Weiping Teng¹⁰, Yushu Li¹¹

Affiliations

¹ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: cuixuewei555@163.com.
² Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: ddd456852@126.com.
³ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: zhaona90126@126.com.
⁴ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: wangshiwei062@163.com.
⁵ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: wangzhen_0527@126.com.
⁶ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: huanghms@163.com.
⁷ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: ping.1990.08@163.com.
⁸ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: qjjiayou@hotmail.com.
⁹ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: cmushanzhongyan@163.com.
¹⁰ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: twp@vip.163.com.
¹¹ Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China. Electronic address: liyushu@hotmail.com.

PMID: 32045626
DOI: 10.1016/j.mce.2020.110756

Abstract

Exosomes have been intensively studied in autoimmune diseases, and circulating exosomes and microvesicles have also been explored in autoimmune thyroiditis (AITD). However, the role of thyroid cell-derived exosomes in immune responses is unclear. We showed that IFN-γ-treated Nthy-ori 3-1 cell-derived exosomes (IFN-γ-Exo) harbored TPO, HSP60 and MHC-II and activated dendritic cells (DCs) in vitro. Compared with Exo-targeted DCs (DC_Exo), IFN-γ-Exo-targeted DCs (DC_IFN-γ-Exo) promoted the expression and release of proinflammatory cytokines, such as IFN-γ, IL-17A and IL-22, from CD4⁺ T lymphocytes and inhibited the expression and release of anti-inflammatory cytokines, such as IL-4, IL-10 and TGF-β1; however, IFN-γ-Exo did not have this effect compared with Nthy-ori 3-1 cell-derived exosomes (Exo). DC_IFN-γ-Exo stimulates the expression and release of cytokines from CD4⁺ T lymphocytes more efficiently than IFN-γ-Exo. Thus, DC_IFN-γ-Exo may effectively induce CD4⁺ T lymphocyte-mediated immune responses and play a role in the occurrence and development of AITD.

Keywords: Dendritic cell; Exosomes; Hashimoto thyroiditis; T lymphocyte; Thyroid cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Autoantigens / metabolism
CD4-Positive T-Lymphocytes / immunology*
Cells, Cultured
Chaperonin 60 / metabolism
Dendritic Cells / drug effects
Dendritic Cells / immunology*
Dendritic Cells / metabolism
Exosomes / drug effects
Exosomes / metabolism*
Exosomes / microbiology*
Female
Histocompatibility Antigens Class II / metabolism
Humans
Interferon-gamma / pharmacology
Iodide Peroxidase / metabolism
Iron-Binding Proteins / metabolism
Lymphocyte Activation / drug effects
Middle Aged
Mitochondrial Proteins / metabolism
Thyroid Epithelial Cells / drug effects
Thyroid Epithelial Cells / metabolism*

Substances

Autoantigens
Chaperonin 60
HSPD1 protein, human
Histocompatibility Antigens Class II
Iron-Binding Proteins
Mitochondrial Proteins
Interferon-gamma
TPO protein, human
Iodide Peroxidase