Treatment of murine lupus with TIGIT-Ig

Shuowu Liu; Lizhu Sun; Chuqi Wang; Yingshu Cui; Yuee Ling; Tian Li; Fangxing Lin; Wenyan Fu; Min Ding; Shuyi Zhang; Changhai Lei; Shi Hu

doi:10.1016/j.clim.2019.04.007

Treatment of murine lupus with TIGIT-Ig

Clin Immunol. 2019 Jun:203:72-80. doi: 10.1016/j.clim.2019.04.007. Epub 2019 Apr 18.

Authors

Shuowu Liu¹, Lizhu Sun², Chuqi Wang¹, Yingshu Cui¹, Yuee Ling³, Tian Li¹, Fangxing Lin⁴, Wenyan Fu⁵, Min Ding³, Shuyi Zhang¹, Changhai Lei¹, Shi Hu⁶

Affiliations

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.

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

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Antinuclear / blood
Disease Models, Animal
Female
Humans
Immunoglobulin Fc Fragments / genetics
Immunoglobulin G / genetics
Immunotherapy / methods*
Lupus Erythematosus, Systemic / immunology
Lupus Erythematosus, Systemic / therapy*
Lupus Nephritis / immunology
Lupus Nephritis / therapy*
Mice
Mice, Inbred NZB
Mice, SCID
Receptors, Immunologic / genetics*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / therapeutic use*

Substances

Antibodies, Antinuclear
Immunoglobulin Fc Fragments
Immunoglobulin G
Receptors, Immunologic
Recombinant Fusion Proteins
T cell Ig and ITIM domain protein, mouse