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Involvement of Inducible Costimulator Ligand (ICOSL) Expression in Thyroid Tissue in Hyperthyroidism of Graves’ Disease Patients

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Abstract

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.

Meterials and Methods

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.

Results and Discussion

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.

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Acknowledgments

We thank Prof. Yibei Zhu for expert suggestions regarding the project and critical comments on the manuscript. We also thank Dr. Shi for her help with the collection of peripheral blood samples. This work was supported by the National Natural Science Foundation of China (No. 30801023, No.81001337, No.31100634 and No.31170834), the key Program of National Science Foundation of China (No. 30930085) and the National Science Foundation for Postdoctoral Scientists of China (No. 20090461140).

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Authors and Affiliations

  1. Institute of Medical Biotechnology, Medical College of Soochow University, 708 Renmin Road, Suzhou, 215007, Jiangsu, China

    Fengming Wang, Lujun Chen, Tong Liu, Shuang Shen, Ting Li, Li Gao, Ting Wang, Jing Sun & Xueguang Zhang

  2. Testing Center, Center for Disease Prevention and Control, Changzhou, 213000, Jiangsu, China

    Fengming Wang

  3. Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215007, Jiangsu, China

    Tao Yan & Haorong Wu

  4. Department of Hepatobiliary Surgery, Tong Ling People’s Hospital, Tongling, 244000, Anhui, China

    Tao Yan

  5. Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China

    Xuemin Chen

  6. Clinical Immunology Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, 215007, Jiangsu, China

    Cuiping Liu

  7. Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215002, China

    Lei Chen

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  1. Fengming Wang
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  2. Tao Yan
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  3. Lujun Chen
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  14. Lei Chen
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Corresponding authors

Correspondence to Xueguang Zhang or Lei Chen.

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Fengming Wang and Tao Yan contributed equally to this work.

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Wang, F., Yan, T., Chen, L. et al. Involvement of Inducible Costimulator Ligand (ICOSL) Expression in Thyroid Tissue in Hyperthyroidism of Graves’ Disease Patients. J Clin Immunol 32, 1253–1261 (2012). https://doi.org/10.1007/s10875-012-9711-2

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  • DOI: https://doi.org/10.1007/s10875-012-9711-2

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