Laboratory for Cytokine Regulation

Helper T (T_H) cells, which play a central role in the effector and regulatory functions in immunologi¬cal surveillance and aberrations of these functions can lead to various immunological disorders. When the immune system encounters a potential threat, antigen-presenting cells deliver chunks of protein from the invading pathogen to naive T cells, and then the cells can differentiate into several subsets of T_H cell that were divided into T_H1, T_H2, T_H17, and T_FH on the basis of their non-overlapping cytokine profiles. The overriding goal of our laboratory is to understand the molecular mechanisms underlying T_H differentiation and the relevance with immunological disorders.

Research Fields

Immunology

Research Subjects

• Transcriptional regulation of cytokines in T helper cells
• Regulation of skin homeostasis by cytokines
• Vaccine development for influenza infection

Publications

1. Okamoto, M., Van, Stry, M., Chung, L., Koyanagi, M., Sun, X., Suzuki, Y., Ohara, O., Kitamura, H., Hijikata, A., Kubo, M., and Bix, M.:
   "Mina, an Il4 repressor, controls T helper type 2 bias."
   Nat. Immunol. 10(8):872-879, 2009.
2. Tanaka, S., Motomura, Y., Suzuki, Y., Yagi, R., Inoue, H., Miyatake, S., Kubo, M.:
   "The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in T_H2 cells. "
   Nat. Immunol. 12(1):77-85, 2011.
3. Motomura, Y., Kitamura, H., Hijikata, A., Matsunaga, Y., Matsumoto, K., Inoue, H., Atarashi, K., Hori, S., Watarai, H., Zhu, J., Taniguchi, M., and Kubo, M.:
   "The transcription factor E4BP4 regulates the production of IL -10 and IL-13 in CD4⁺　T cells."
   Nat. Immunol. 12(5):450-459, 2011.
4. Siracusa, M. C., Saenz, S. A., Hill, D. A., Kim, B. S. Headley, M. B., Doering, T. A., Wherry, E.J., Jessup, H. K., Siegel, L. A., Kambayashi, T., Dudek, E. C., Kubo, M., Cianferoni, A., Spergel, J. M., Ziegler, S. F., Comeau, M. R., and Artis, D.:
   "TSLP promotes interleukin-3-independent basophil hematopoiesis and type 2 inflammation.
   Nature 477(7363):229-233, 2011."
5. Sawaguchi, M., Tanaka, S., Nakatani, Y., Harada, Y., Mukai, K., Matsunaga, Y., Ishiwata, K., Oboki, K., Kambayashi, T., Watanabe, N., Karasuyama, H., Nakae, S., Inoue, H., and Kubo, M.:
   "Role of mast cells and basophils in IgE responses and in allergic airway hyperresponsiveness."
   J. Immunol. 188(4):1809-1818, 2012.
6. Harada, Y., Tanaka, S., Motomura, Y., Harada, Y., Ohno, S., Ohno, S., Yanagi, Y., Inoue, H., and Kubo, M.:
   "The 3′ Enhancer CNS2 is a Critical Regulator of Interleukin-4-Mediated Humoral Immunity in Follicular Helper T Cells."
   Immunity. 36(2):188-200, 2012.
7. Hill, D.A., Siracusa, M.C., Abt, M.C., Kim, B.S., Kobuley, D., Kubo, M., Kambayashi, T., Larosa, D.F., Renner, E.D., Orange, J.S., Bushman, F.D., and Artis D.:
   "Commensal bacterial–derived signals regulate basophil hematopoiesis and allergic inflammation."
   Nat. Med. 18(4):538-546, 2012.
8. Uto-Konomi, A., Miyauchi, K., Ozaki, N., Motomura, Y., Suzuki, Y., Yoshimura, A., Suzuki, S., Cua, D., and Kubo, M.:
   "Dysregulation of suppressor of cytokine signaling 3 in keratinocytes causes skin inflammation mediated by interleukin-20 receptor-related cytokines."
   PLoS One. 7(7):e40343, 2012.
9. Kubo, M. & Motomura, Y.:
   "Transcriptional regulation of anti-inflammatory cytokine, IL-10 in acquired immune cells."
   Front. Immunol. 3:275, 2012.
10. Kaji, T., Ishige, A., Hikida, M., Taka, J., Hijikata, A., Kubo, M., Nagashima, T., Takahashi, Y., Kurosaki, T., Okada, M., Ohara, O., Rajewsky, K., Takemori, T.:
    "Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory."
    J. Exp. Med. 209(11):2079-2097, 2012.