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Clin Immunol. 2019 Apr 18;203:72-80. doi: 10.1016/j.clim.2019.04.007. [Epub ahead of print]

Treatment of murine lupus with TIGIT-Ig.

Author information

1
Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China; Team SMMU-China of International Genetically Engineered Machine (iGEM) competitions, Department of Biophysics, Second Military Medical University, Shanghai 200433, China.
2
Department of Emergency Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
3
Pharchoice Therapeutics Inc., Shanghai 201406, China.
4
Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China.
5
Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
6
Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China; Team SMMU-China of International Genetically Engineered Machine (iGEM) competitions, Department of Biophysics, Second Military Medical University, Shanghai 200433, China. Electronic address: hus@smmu.edu.cn.

Abstract

The TIGIT (T cell immunoreceptor with Ig and ITIM domains) protein is a co-inhibitory receptor that has been reported to suppress autoreactive T and B cells to trigger immunological tolerance. We generated a new recombinant protein by connecting the extracellular domain of murine TIGIT to the Fc region of the mouse immunoglobulin IgG2a. The fusion protein was then characterized. The results suggested that among mice with lupus that were treated with the TIGIT-Ig fusion protein, the onset of proteinuria was delayed, serum concentrations of autoantibodies, such as antinuclear antibodies, were reduced without a decrease in the total IgG concentrations, and the survival rate was significantly increased compared to those of the controls. In conclusion, TIGIT-Ig administration showed promising results for both the prevention and treatment of autoimmune diseases in mice. This indicates that treatment with recombinant human TIGIT-Ig shows promise as an effective way to treat human autoimmune diseases.

KEYWORDS:

Murine lupus; Targeted therapy; Tigit

PMID:
31005675
DOI:
10.1016/j.clim.2019.04.007

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