title: Increased IL-21/IL-21R expression and its proinflammatory effects in autoimmune thyroid disease.
abstract: To determine the potential role of interleukin-21 (IL-21) / IL-21 receptor (IL-21R) in the pathogenesis of autoimmune thyroid disease (AITD) mainly known as Graves' disease (GD) and Hashimoto's thyroiditis (HT). IL-21 and IL-21R of peripheral blood samples and/or thyroid tissues from AITD patients and healthy controls were analyzed by ELISA, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry and immunohistochemistry. In vitro, the mRNA and protein of inflammatory cytokines of cultured peripheral blood mononuclear cells (PBMCs) upon recombinant human IL-21 (rhIL-21) stimulation were detected. There was an increased serum concentration of IL-21 in untreated GD and HT patients, and IL-21(+)CD3(+)CD8(-)T cells were significantly increased in PBMCs of HT patients compared with healthy volunteers. The IL-21 mRNA expression in PBMCs increased dramatically in GD and HT patients, and marked augmentations of IL-21 and IL-21R mRNA in thyroid tissues of HT patients were observed. Immunohistochemical staining confirmed the expression of IL-21R protein in HT thyroid cells and lymphocytes. In vitro, PBMCs from GD cultured with rhIL-21 induced increased IL-17A but decreased IL-4 production, while from HT stimulated by rhIL-21 induced augmented production of IFN-γ. In conclusion, the expression of IL-21 and IL-21R were up-regulated in AITD and may be involved in the pathogenesis of the disease through augmenting aberrant immune cascade.
authors: The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Li-juan
authors: LJ
authors: Guan
authors: The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710061, China; Endocrinology Department, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors: Xuan
authors: X
authors: Wang
authors: Endocrinology Department, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors: Shuai
authors: S
authors: Meng
authors: Endocrinology Department, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors: Liang-feng
authors: LF
authors: Shi
authors: Endocrinology Department, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors: Wen-juan
authors: WJ
authors: Jiang
authors: Endocrinology Department, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors: Ling
authors: L
authors: Xiao
authors: Endocrinology Department, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors: Xiao-hong
authors: XH
authors: Shi
authors: Endocrinology Department, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors: Jian
authors: J
authors: Xu
authors: Endocrinology Department, Jinshan Hospital of Fudan University, Shanghai 201508, China. Electronic address: zhangjinan@hotmail.com.
authors: Jin-an
authors: JA
authors: Zhang
mesh_terms: D000328:Adult; D005434:Flow Cytometry; D006111:Graves Disease / Q000276:immunology*; D050031:Hashimoto Disease / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D053655:Receptors, Interleukin-21 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013961:Thyroid Gland / Q000276:immunology / Q000648:ultrastructure; D000098546:Interleukin-21
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D053655:Receptors, Interleukin-21; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D000098546:Interleukin-21
keywords: Autoimmune thyroid disease (AITD); Graves’ disease (GD); Hashimoto’s thyroiditis (HT); Interleukin-21 (IL-21); Interleukin-21 receptor (IL-21R)