Staff

Professor: Koji Tokoyoda, Ph.D. tokoyoda@tottori-u.ac.jp
Associate professor: Miya Yoshino, D.D.S., Ph.D. myoshi@tottori-u.ac.jp
Assistant professor: Akihiko Murata,Ph.D. muratako@tottori-u.ac.jp

Features of the Division

Memory T helper cells and long-lived ‘memory’ plasma cells are critical for long-lasting humoral immune memory to infectious pathogens and autoantigens. Despite their central role, how the memory cells are generated and maintained in the body still remains unclear. We aim at understanding the dynamics of memory T helper cells and memory plasma cells during immune response(s) and the mechanisms of their survival on a molecular level.
Recently, we have found and further described the microenvironment ‘niches’ for survival of memory T helper cells and memory plasma cells. Memory T helper cells and memory plasma cells reside in IL-7+collagen-XI+ and CXCL12+ stromal cells of the bone marrow, respectively. Although it had been commonly thought that memory T helper cells are circulating and need the presence of antigen, our results show that protective memory T helper cells are not circulating and instead reside and rest in the bone marrow in an antigen-independent manner. We have also reported that CD49b (integrin alpha2), CD69 (a C-type lectin) and Myosin light chain 9/12 (a ligand of CD69) are required for the generation and maintenance of protective memory T helper cells in the bone marrow and that CD49b+T-bet/CXCR3+ activated CD4 T cells generated during the primary immune response are the precursors of memory T helper cells in the bone marrow. Most recently we could describe an unexpected mechanism by which Salmonella regulate IgG-secreting memory plasma cells in the bone marrow.
The detailed knowledge of the molecules and signals involved in the maintenance of memory cells is crucial for the development of new therapies specifically targeting these cells in autoimmune diseases.

Selected Publication
1. Takaya A et al. Front Immunol 10:3155, 2020.
2. Sarkander J et al. Front Immunol 10:3113, 2020.
3. Männe C et al. Proc Natl Acad Sci USA 116:7425-7430, 2019.
4. Sarkander J et al. Clin Transl Immunol 5:e120, 2016.
5. Hayashizaki K et al. Sci Immunol 1:eaaf9154, 2016.
6. Hojyo S et al. Front Immunol 7:26, 2016.
7. Hanazawa A et al. Front Immunol 4:183, 2013.
8. Hanazawa A et al. Immunol Cell Biol 91:524-531, 2013.
9. Tokoyoda K et al. Cell Mol Life Sci 69:1609-1613, 2012.
10. Shinoda K et al. Proc Natl Acad Sci USA 109:7409-7414, 2012.
11. Tokoyoda K et al. Nat Rev Immunol 10:193-200, 2010.
12. Tokoyoda K et al. Eur J Immunol 39:2095-2099, 2009.
13. Tokoyoda K et al. Immunity 30:721-730, 2009.
14. Tokoyoda K et al. Immunity 20:707-718, 2004.
15. Tokoyoda K et al. Int Immunol 16:643-653, 2004.