DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions

• DOI: 10.1073/pnas.2021309118
• Publication Date: 2021-05-19T19:36:31Z
• Authors: Kazuki Sato; Yumi Yamashita-Ka...; Fumie Abe; Rikito Murata; Yuho Nakamura-Shinya; Kazumasa Kanemaru; Masafumi Muratani; André Veillette; Motohito Goto; Mamoru Ito; Akira Shibuya; Kazuko Shibuya
• Keywords: Antigens, Differentiation, T-Lymphocyte; 0301 basic medicine; Mice, Inbred BALB C; TOR Serine-Threonine Kinases; Graft vs Host Disease; Forkhead Transcription Factors; Adoptive Transfer; T-Lymphocytes, Regulatory; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Gene Expression Regulation; Immune Tolerance; Animals; Humans; Receptors, Virus; Receptors, Immunologic; Proto-Oncogene Proteins c-akt; Whole-Body Irradiation; Protein Binding; Signal Transduction

Significance Immune tolerance is essential to prevent autoimmune responses, but it often needs to be limited for proper immune response. Regulatory T (Treg) cells play a crucial role in immune tolerance; however, their immune-suppressive function is restricted under inflammatory conditions. Here, we show that the activated immune receptor DNAM-1 limits Treg cell function regardless of DNAM-1–mediated intracellular signaling. We found that DNAM-1 competes with T cell immunoreceptor with Ig and ITIM domains (TIGIT) in binding to a common ligand. DNAM-1 deficiency enhances TIGIT signaling, thus resulting in the Treg cell function’s maintenance under inflammatory conditions. These results suggest that the DNAM-1 and TIGIT balance orchestrate Treg cell function for optimal immune reaction.