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Defective expression of regulatory B cells in iodine-induced autoimmune thyroiditis in non-obese diabetic H-2h4 mice

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Abstract

Introduction

The ability of B cells to negatively regulate cellular immune responses and inflammation has been described. The regulatory B (Breg) cells with the unique CD1dhiCD5+CD19+ phenotype and the capacity to produce IL-10 are potent negative regulators of inflammation and autoimmunity in several in vivo mouse models of autoimmune disease.

Aim

To investigate whether Breg cell deficiency participates in autoimmune thyroiditis (AIT) in an animal model.

Materials and methods

Non-obese diabetic (NOD).H-2h4 mice at 4 weeks of age were randomly divided into control and iodine-treated groups; the iodine-treated group received sterile water containing 0.005 % NaI for 10 or 20 weeks. The percentage of CD1dhiCD5+CD19+ Bregs, CD4+CD25+FoxP3+ regulatory T cells (Treg) and CD4+IL17+ T helper 17 cells (Th17) in splenic mononuclear cells was detected by multicolor flow cytometry. The expression of IL-10 mRNA and TGF-β mRNA in splenocytes was measured by real-time RT-PCR.

Results

NOD.H-2h4 mice spontaneously develop anti-thyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in drinking water. Mice with AIT had a decreased CD1dhiCD5+CD19+ Breg subset and reduced IL-10 mRNA expression in splenocytes compared with controls (p < 0.05) and maintained relatively low levels during the development of thyroiditis. The proportion of Breg cells was negatively correlated with the proportion of Th17 cells, but positively correlated with CD4+CD25+FoxP3+ Treg cells in splenocytes (All p < 0.05).

Conclusions

The defective expression of Breg cells combined with impaired Treg cells and enhanced Th17 cells might play an important role in the development of iodine-induced AIT in NOD.H-2h4 mice.

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Abbreviations

AIT:

Autoimmune thyroiditis

NOD.H-2h4 :

Non-obese diabetic H-2h4

Treg:

Regulatory T cells

Breg:

Regulatory B cells

SAT:

Spontaneously developed autoimmune thyroiditis

Th1:

T helper type 1

Th2:

T helper type 2

EAE:

Experimental autoimmune encephalitis

RA:

Rheumatoid arthritis

CIA:

Collagen-induced arthritis

TgAb:

Anti-thyroglobulin antibody

MTg:

Mouse thyroglobulin

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Acknowledgments

We thank Ms. Hongmei Zhang and Ms. Hong Wang for their excellent technical assistance. This project was supported by a research fund from the National Nature Science Foundation of China (81170731).

Conflict of interest

The authors Lei Shi, Mei Bi, Rong Yang, ** Zhou, Shujie Zhao, Chenling Fan, Zhongyan Shan, Yushu Li, and Wei** Teng declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Authors and Affiliations

  1. Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China

    L. Shi

  2. Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, No.155 Nan**g Bei St., He** District, Shenyang, 110001, People’s Republic of China

    L. Shi, M. Bi, R. Yang, J. Zhou, S. Zhao, C. Fan, Z. Shan, Y. Li & W. Teng

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  1. L. Shi
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  2. M. Bi
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  5. S. Zhao
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  6. C. Fan
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  7. Z. Shan
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Correspondence to Y. Li or W. Teng.

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Y. Li and W. Teng have contributed equally to this manuscript.

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Shi, L., Bi, M., Yang, R. et al. Defective expression of regulatory B cells in iodine-induced autoimmune thyroiditis in non-obese diabetic H-2h4 mice. J Endocrinol Invest 37, 43–50 (2014). https://doi.org/10.1007/s40618-013-0013-1

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