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Immunology

Overview

The basic research focus in the Department is Immunology, particularly the immunological memory including “inflammatory memory”. Especially, we focus on how tissue-resident memory CD4+ T cells differentiate and persist over a long time in the inflamed tissues. We also conduct model studies on various diseases including chronic airway inflammation, and translational research on allergic disorders in collaboration with clinical doctors at Chiba University Hospital.
The educational goal of the Department is to “cultivate professional researchers” .
We hope to create a global research environment where we can discover principles associated with the control of immunological memory as well as present and verify new treatment concepts in translational research. Thus, we try to contribute to significant developments in immunological research through the international collaboration with the University of California, San Diego and National Institutes of Health (NIH) in the United States, and Deutsches Rheuma-Forschungzentrum Berlin in Germany.

Professor:
Kiyoshi Hirahara, M.D., Ph.D.

TEL: +81-43-226-2200
FAX: +81-43-227-1498
e-mail: hiraharak●chiba-u.jp
URL: https://www.m.chiba-u.ac.jp/dept/meneki/

※　Please change "●" mark to at-mark if you send emails.

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Research & Education

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  1. Generation and Maintenance of Immune system
    1) Generation and maintenance of tissue resident memory CD4+ T cells
    2) Induction and maintenance of memory-type “pathogenic” Th2 (Tpath2) cells
    3) Generation and maintenance of ectopic lymphoid tissue in the inflamed tissue
    4) Epigenetic regulation of memory Th2 cells

  2. Regulation of Intractable Pathologies during Allergic Inflammation
    (Asthma, Chronic Rhinosinusitis, Conjunctivitis)
    1) Regulation of Fibrotic Responses: Molecular studies in mouse models
    2) Pathophysiology of Eosinophilic chronic rhinosinusitis (ECRS)
    3) Elucidation of Pathogenic Itch: Neuro-Immune Interaction

Recent Publications

  1. Morimoto, Y.,* Hirahara, K.,* Kiuchi, M., Wada, T., Ichikawa, T., Kanno, T., Okano, M., Kokubo, K., Onodera, A., Sakurai, D., Okamoto, Y., and Nakayama, T.: Amphiregulin-producing pathogenic memory T helper-2 cells instruct eosinophils to secrete osteopontin and facilitate airway fibrosis. (*These authors contributed equally to this work) Immunity 49(1):134-150.e6 (2018).
  2. Ichikawa, T.,* Hirahara, K.,* Kokubo, K.,* Kiuchi, M., Aoki, A., Morimoto, Y., Kumagai, J., Onodera, A., Mato, N., Tumes, D. J., Goto, Y., Hagiwara, K., Inagaki, Y., Sparwasser, T., Tobe, K., and Nakayama, T.: CD103hi Treg cells constrain lung fibrosis induced by CD103lo tissue-resident pathogenic CD4 T cells. (*These authors contributed equally to this work) Nat. Immunol. 20(11):1469-1480 (2019).
  3. Okano, M., Hirahara, K., Kiuchi, M., Onoue, M., Iwamura, C., Kokubo, K., Hishiya, T., Morimoto, Y., Ikehara, Y., Murakami, A., Ebihara, N., and Nakayama, T.: Interleukin-33-activated neuropeptide CGRP-producing memory Th2 cells cooperate with somatosensory neurons to induce conjunctival itch. Immunity 55(12):2352-2368.e7 (2022).
  4. Kokubo, K., Hirahara, K., Kiuchi, M., Tsuji, K., Shimada, Y., Sonobe, Y., Shinmi, R., Hishiya, T., Iwamura, C., Onodera, A., and Nakayama, T.: Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism. Proc. Natl. Acad. Sci. USA 120(2):e2218345120 (2023).
  5. Sato, Y., Silina, K., van den Broek, M., Hirahara, K., and Yanagita, M.: The roles of tertiary lymphoid structures in chronic diseases. Nat. Rev. Nephrol. 19:525-537 (2023).
  6. Kumagai, J., Kiuchi, M., Kokubo, K., Yagyu, H., Nemoto, M., Tsuji, K., Nagahata, K., Sasaki, A., Hishiya, T., Onoue, M., Shinmi, R., Sonobe, Y., Iinuma, T., Yonekura, S., Shinga, J., Hanazawa, T., Koseki, H., Nakayama, T., Yokote, K., and Hirahara, K.: The USP7-STAT3-granzyme-Par-1 axis regulates allergic inflammation by promoting differentiation of IL-5-producing Th2 cells. Proc. Natl. Acad. Sci. USA 120(49):e2302903120 (2023).