Professor（Specially appointed for research） Toshiyuki TAKAI, PhD [Researchmap]
Researcher Yuting XIE, PhD
Technical Assistant Kayoko HAYASHI
Secretarial Assistant Takako NAKAMURA
Guest Instructor Yuzuru SAKAMOTO
Guest Researcher Mei-Tzu SU, PhD
Guest Researcher Masanori INUI, PhD

We aim at discovering novel drugs targeting FAIN.
On April 1st, 2023, we have started our new Department of Experimental Immunology laboratory, the past of which has 25-years history since 1997. In the past, we investigated the mechanism of immune regulation by positive and negative immunoreceptors such as Fc receptors and LILR family receptors (1–4). Our new laboratory has started to develop novel drugs to treat cancer, autoimmune, and neuronal diseases. The target molecules are Focal Adhesion Integrin Inhibitors (FAIN), which down regulate integrin-mediated cellular functions, such as inflammation, growth, development, and movement (5–11) (Fig. 1).

1. Takai T. Roles of Fc receptors in autoimmunity. Nat Rev Immunol. 2002 Aug;2(8):580-92. doi: 10.1038/nri856.
2. Takai T, Nakamura A, Endo S. Role of PIR-B in autoimmune glomerulonephritis. J Biomed Biotechnol. 2011;2011:275302. doi: 10.1155/2011/275302.
3. Inui M, Sugahara-Tobinai A, Fujii H, Itoh-Nakadai A, Fukuyama H, Kurosaki T, Ishii T, Harigae H, Takai T. Tolerogenic immunoreceptor ILT3/LILRB4 paradoxically marks pathogenic auto-antibody-producing plasmablasts and plasma cells in non-treated SLE. Int Immunol. 2016 Dec;28(12):597-604. doi: 10.1093/intimm/dxw044.
4. Koga T, Inui M, Inoue K, Kim S, Suematsu A, Kobayashi E, Iwata T, Ohnishi H, Matozaki T, Kodama T, Taniguchi T, Takayanagi H, Takai T. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature. 2004 Apr 15;428(6984):758-63. doi: 10.1038/nature02444.
5. Su MT, Kumata S, Endo S, Okada Y, Takai T. LILRB4 promotes tumor metastasis by regulating MDSCs and inhibiting miR-1 family miRNAs. Oncoimmunology. 2022 Apr 5;11(1):2060907. doi: 10.1080/2162402X.2022.2060907.
6. Su MT, Inui M, Wong YL, Takahashi M, Sugahara-Tobinai A, Ono K, Miyamoto S, Murakami K, Itoh-Nakadai A, Kezuka D, Itoi S, Endo S, Hirayasu K, Arase H, Takai T. Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin ameliorates autoimmune disease in BXSB/Yaa mice. Int Immunol. 2021 Jul 23;33(8):447-458. doi: 10.1093/intimm/dxab028.
7. Immune Checkpoint Inhibitors.
8. Itoi S, Takahashi N, Saito H, Miyata Y, Su MT, Kezuka D, Itagaki F, Endo S, Fujii H, Harigae H, Sakamoto Y, Takai T. Myeloid immune checkpoint ILT3/LILRB4/gp49B can co-tether fibronectin with integrin on macrophages. Int Immunol. 2022 Jul 26;34(8):435-444. doi: 10.1093/intimm/dxac023.
9. Takahashi N, Itoi S, Su MT, Endo S, Takai T. Co-localization of Fibronectin Receptors LILRB4/gp49B and Integrin on Dendritic Cell Surface. Tohoku J Exp Med. 2022 Jun 25;257(3):171-180. doi: 10.1620/tjem.2022.J014.
10. Su MT, Ono K, Kezuka D, Miyamoto S, Mori Y, Takai T. Fibronectin-LILRB4/gp49B interaction negatively regulates osteoclastogenesis through inhibition of RANKL-induced TRAF6/TAK1/NF-kB/MAPK signaling. Int Immunol. 2023 Mar 14;35(3):135-145. doi: 10.1093/intimm/dxac051.
11. Miyamoto S, Chiba T, Itoi S, Su MT, Takai T. LILRB4/gp49B Co-Localizes with Integrin via Fibronectin at Focal Adhesion Sites on Mast Cells. Tohoku J Exp Med. 2023 Mar 10;259(4):273-284. doi: 10.1620/tjem.2023.J001.

Fig. 1 LILRB4 is a FAIN