Multiple sclerosis (MS) is an autoimmune disease caused by immune cells, including T cells and B cells. In MS patients, the number and function of regulatory T cells (Tregs) that maintain immune homeostasis are reduced. Therefore, inducing Treg cells in MS patients can be a critical therapeutic strategy, but Treg-inducing drugs have not been approved yet. 

CTLA-4 is an immune checkpoint molecule inhibits T cell activation and is required for Treg function. However, it is not known whether CTLA-4 signaling can induce Treg cells from naive T cells.

Je-Min Choi’s group developed a therapeutic peptide derived from CTLA-4 protein and found that the signaling peptide induces Treg cells from both murine and human T cells and confirmed its funciton in mouse models of MS. The study was published in the ‘Advanced Science’ in July 21st 2021.

In the mouse model of MS, CTLA-4 peptide inhibits disease progression by increasing Treg cells and decreasing disease-causing pathogenic T cells like Th1 and Th17 cells in the spinal cord. Although treatment of CTLA-4 peptide is stopped, it still prevents disease relapse up to 100 days by inducing Treg cells. In addition, CTLA-4 peptide increases Treg cells in blood cells from healthy humans and MS patients, and in humanized mouse system in vivo.

These studies suggest that CTLA-4 peptide would be a novel therapeutic agent to induce regulatory T cells to control autoimmune disease like Multiple Sclerosis. For the development of peptide drugs for clinical trials, Je-Min Choi’s group is finalizing pre-clinical study to improve the therapeutic efficacy and stability with less toxicity.

This work is supported by the Bio and Medical Technology Development Program, and the Basic Science Research Program, and the Original Technology Research Program for Brain Science of the National Research Foundation funded by the Korean government. It is published in Advanced Science (July 21st, 2021) and the topic is selected as a cover image.

[Reference] Gil-Ran Kim et al. Advanced Science (2021 July 21st) “In vivo induction of regulatory T cells via CTLA-4 signaling peptide to control autoimmune encephalomyelitis and prevent disease relapse” 

[Main Author] Gil-Ran Kim (Hanyang University), Won-Ju Kim (Hanyang University), Sangho Lim (Hubrecht Institute), and Je-Min Choi (Hanyang University)* 

* Contact : Prof. Je-Min Choi (jeminchoi@hanyang.ac.kr)