Anti-human-TIGIT agonistic antibody ameliorates autoimmune diseases by inhibiting Tfh and Tph cells and enhancing Treg cells

• Published in: Communications biology Vol. 6; no. 1; pp. 500 - 13
• Main Authors: Kojima, Marenori, Suzuki, Katsuya, Takeshita, Masaru, Ohyagi, Masaki, Iizuka, Mana, Yamane, Humitsugu, Koga, Keiko, Kouro, Taku, Kassai, Yoshiaki, Yoshihara, Tomoki, Adachi, Ryutaro, Hashikami, Kentarou, Ota, Yuichiro, Yoshimoto, Keiko, Kaneko, Yuko, Morita, Rimpei, Yoshimura, Akihiko, Takeuchi, Tsutomu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.05.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 64/60; 692/4023/1670/1613; 692/4023/1670/498; Agonistic behavior; Animals; Antibodies, Monoclonal - pharmacology; Autoimmune diseases; Autoimmune Diseases - drug therapy; Biology; Biomedical and Life Sciences; CD4 antigen; Cell activation; Immunoglobulins; Immunoreceptor tyrosine-based inhibition motif; Immunoregulation; Life Sciences; Lymphocytes; Lymphocytes T; Mice; Monoclonal antibodies; Receptors, Immunologic - genetics; Signal Transduction; T-Lymphocytes, Regulatory
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-023-04874-3

T cells play important roles in autoimmune diseases, but it remains unclear how to optimally manipulate them. We focused on the T cell immunoreceptor with Ig and ITIM domains (TIGIT), a coinhibitory molecule that regulates and is expressed in T cells. In autoimmune diseases, the association between TIGIT-expressing cells and pathogenesis and the function of human-TIGIT (hu-TIGIT) signalling modification have not been fully elucidated. Here we generated anti-hu-TIGIT agonistic monoclonal antibodies (mAbs) and generated hu- TIGIT knock-in mice to accurately evaluate the efficacy of mAb function. Our mAb suppressed the activation of CD4 + T cells, especially follicular helper T and peripheral helper T cells that highly expressed TIGIT, and enhanced the suppressive function of naïve regulatory T cells. These results indicate that our mAb has advantages in restoring the imbalance of T cells that are activated in autoimmune diseases and suggest potential clinical applications for anti-hu-TIGIT agonistic mAbs as therapeutic agents. A monoclonal human T cell immunoreceptor with Ig and ITIM domains (TIGIT) agonistic antibody in a TIGIT knock-in mouse model suppresses follicular and peripheral helper T cell activation and enhances suppression effects of naive regulatory T cells.