Basic Medicine, Immunology
To Understand the Molecular Mechanisms for Discrimination between Immunological Self and Non-self and Memory Based on Immunoregulatory Receptors of Lymphocytes
Medical Sciences Course
- Master / Doctoral Degree
- TAKAI, Toshiyuki
toshiyuki.takai.b8*tohoku.ac.jp (Please convert "*" into "@".)
- Immunoregulatory receptors on B lymphocytes in maintaining tolerance and immunological memory
- Deregulated B cell tolerance in autoimmune diseases such as systemic lupus erythematosus
- Development of therapeutic ligands for immunoregulatory receptors for treating allergic and autoimmune diseases
immune regulation, B lymphocyte, immunological tolerance, immunological memory, cell-surface receptor protein
gene-engineered mice, flow cytometric fine sorting of human peripheral blood cells, allergy/inflammation/autoantibody, in vitro B cell development, in vitro molecular evolution technique
The Laboratory of Experimental Immunology aims to understand the molecular mechanisms by which our immune system discriminates between immunological self and non-self, based on our detailed analysis of immunoregulatory receptors on various cells such as B cells and T cells. We, for the first time, discovered the importance of immunoregulatory receptors (Takai T. Nat. Rev. Immunol. 2:580, 2002; Nakamura A. et al. Nat. Immunol. 5:623, 2004). Studies are now in progress on the roles of immunoregulatory receptors including FcR and PirB/LILRB in allergy and autoimmune diseases. Development of novel strategies against these immune disorders has also been in progress. Our particular interest is now in 1) elucidating the molecular mechanism of development of autoreactive B cells and generation of autoantibodies in various autoimmune diseases of humans as well as in mouse models, and in 2) regulating the deregulated B cells by generating novel strategies such as development of synthetic ligands for the receptors, generated by the In-Vitro Evolution technique.
Figure 1. Genes for FcγRIIB and SLAM family proteins are juxtaposed
Figure 2. Synergy of FcγRIIB deficiency (RIIB???) and SLAM129 augments autoantibody production
- Kanari Y, et al. Dichotomy in the FcγRIIB deficiency and autoimmune-prone SLAM haplotype clarifies the roles of the Fc receptor in development of autoantibodies and glomerulonephritis. BMC Immunol 2014, 15:47.
- Mitsuhashi Y, et al. Regulation of plasmacytoid dendritic cell responses by PIR-B. Blood 120: 3256-9. 2012.
- Matsushita H, et al. Differential but competitive binding of Nogo protein and class I major histocompatibility complex (MHCI) to the PIR-B ectodomain provides an inhibition of cells. J. Biol. Chem. 2011; 286(29):25739-47.
- Arita K, et al. Transcriptional activation of the Pirb gene in B cells by PU.1 and Runx3. J. Immunol. 2011; 186(12): 7050-9.
- Kubo T, et al. Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity. J. Exp. Med. 2009; 206: 1971-82.