Immunobiology (Satoshi TANAKA)

Immunobiology Satoshi TANAKA, PhD

Major Areas of Research

1. Differentiation and maturation of mast cells
2. Physiological roles of tissue mast cells
3. Histamine-mediated modulation of immune responses
4. MHC-II-mediated antigen presentation in dedritic cells

Current Research Interests

Mast cells are distributed ubiquitously in the body. Previous studies have demonstrated that mast cells play critical roles in immediate allergic response and intestinal parasitic infection. However, the physiological roles of mast cells remain to be determined. Mast cells originate in hematopoietic stem cells and their terminal differentiation occurs in the tissues where they would ultimately reside, indicating that the local microenvironment would have a strong influence on the nature of tissue mast cells. Our goal is to clarify the physiological roles of tissue mast cells, with a focus on the interaction between mast cells and their microenvironment. Accumulating evidence has indicated that mast cells have the potential to respond to a wide variety of stimuli and can make a significant contribution to the maintenance of local homeostasis. It is fascinating to determine when and how mast cells are activated and participate in the regulation of immune/inflammatory reactions.

Recent Research Progress

1. We have revealed that histamine synthesis is induced in mast cells upon sensitization with certain IgE clones. The IgE-mediated activation of mast cells in the absence of antigen has attracted much attention in the field of inflammation and immunity, because this “monomeric IgE effects” may be associated with chronic inflammation characterized by elevated IgE levels.
2. We have established a murine mast cell culture model for cutaneous mast cells, in which bone marrow-derived cultured mast cells are co-cultured with a fibroblastic cell line in the presence of stem cell factor, and identified the gene expression profile during the maturation of mast cells. One of the up-regulated genes during maturation, CD44, was found to regulate the number of mast cells in murine cutaneous tissues. Furthermore, a transient induction of histamine synthesis during the mast cell maturation was found to enhance the granule maturation.

Selected Recent Publications

1. Histamine synthesis is required for granule maturation of murine mast cells. Nakazawa, S., Sakanaka, M., Furuta, K., Natsuhara, M., Takano, H., Tsuchiya, S., Okuno, Y., Ohtsu, H., Nishibori, M., Thurmond, R. L., Hirasawa, N., Nakayama, K., Ichikawa, A., Sugimoto, Y., and Tanaka, S. Eur. J. Immunol. 44, 204-214 (2014)
2. Restriction of mast cell proliferation through hyaluronan synthesis by co-cultured fibroblasts. Takano, H., Furuta, K., Yamashita, K., Sakanaka, M., Itano, N., Gohda, E., Nakayama, K., Kimata, K., Sugimoto, Y., Ichikawa, A., and Tanaka, S. Biol. Pharm. Bull. 35, 408-412 (2012)
3. Takano, H., Nakazawa, S., Shirata, N., Tamba, S., Furuta, K., Tsuchiya, S., Morimoto, K., Itano, N., Irie, A., Kimata, K., Nakayama, K., Sugimoto, Y., and Tanaka, S. Involvement of CD44 in mast cell proliferation during terminal differentiation. Lab. Invest. 89, 446-455 (2009)
4. Takano, H., Nakazawa, S., Okuno, Y., Shirata, N., Tsuchiya, S., Kainoh, T., Takamatsu, S., Furuta, K., Taketomi, Y., Naito, Y., Takematsu, H., Kozutsumi, Y., Tsujimoto, G., Murakami, M., Kudo, I., Ichikawa, A., Nakayama, K., Sugimoto, Y., and Tanaka, S. Establishment of the culture model system that reflects the process of terminal differentiation of connective tissue-type mast cells. FEBS Lett. 582, 1444-1450 (2008)
5. Tanaka, S. Targeting CD44 in mast cell regulation (Review). Expert Opin. Ther. Targets 14 (1), 31-43 (2010)