Involvement of inducible costimulator ligand (ICOSL) expression in thyroid tissue in hyperthyroidism of Graves' disease patients.
BACKGROUND
The role of costimulatory molecules expressed on lymphocytes and thyrocytes in hyperthyroidism has attracted increasing attention and research has shown a close correlation between variant expression of these molecules on lymphocytes and thyrocytes and the development of GD.


METHODS
[corrected] Thyroid tissues were collected from GD patients during surgery and from Hashimoto disease (HT) and non-toxic goiter (NTG) patients as controls. ICOSL expression on infiltrated B cells and TFC was detected by flow cytometry (FCM), reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Variation in ICOSL expression on TFC in primary cultures was analyzed in the absence or presence of cytokines using FCM assays. The role of ICOS-ICOSL signaling in proliferation, thyroid hormone production and thyroglobulin (Tg) release was investigated in primary TFC cultures using ICOS gene transfected L929 cells (ICOS-L929 cells) and the blocking ICOSL antibody (11 C4) in MTT assays and radioimmunoassays.


CONCLUSIONS
ICOSL expression on infiltrated B cells and TFC was detected in GD patient tissue. However, ICOSL expression was only detected on infiltrated B cells in control HT and NTG patient tissue. ICOSL expression on TFC was induced in vitro by the proinflammatory cytokines IFN-γ, IL-6 and TNF-α. Compared with mock transfected L929 (mock-L929) control cells, ICOS-L929 cells promoted significant proliferation of primary cultured TFC, with increased thyroid hormone and Tg production (all P < 0.01). TFC proliferation and production of thyroid hormones and Tg were inhibited significantly in the presence of ICOSL blocking antibody (11 C4) (all P < 0.05). Our observations suggest that ICOS-ICOSL signal plays a direct role in proliferation and differentiation of TFC and may exert important effects in the initiation, maintenance and exaggeration of autoimmune responses in local tissue.
Institute of Medical Biotechnology, Medical College of Soochow University, 708 Renmin Road, Suzhou, 215007, Jiangsu, China.
Fengming
F
Wang
Tao
T
Yan
Lujun
L
Chen
Xuemin
X
Chen
Tong
T
Liu
Shuang
S
Shen
Ting
T
Li
Li
L
Gao
Ting
T
Wang
Jing
J
Sun
Cuiping
C
Liu
Haorong
H
Wu
Xueguang
X
Zhang
Lei
L
Chen
D000328:Adult; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006043:Goiter, Endemic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050031:Hashimoto Disease / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000187:drug effects; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000906:Antibodies; C498514:ICOSLG protein, human; C508600:IL6 protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma