Division and Department

Department of Medical Biology

A Greeting from the Professor

We humans have immune constitution which determines susceptibility of diseases. Some people are infected with influenza virus every year, others are allergic to house dust, pollen, and many types of foods. Apparently, we have immunological traits which predispose us to certain diseases. Our lab is interested in such predisposing factors attributed to innate lymphoid cells (ILCs). ILCs reside in tissues and are responsible for innate cytokine production which determines the type of immune responses. Immune reactions are traditionally classified into type I, type II, and type III immunity. When host cells are infected with intracellular pathogens such as viruses, Listeria monocytogenes, Chlamydia trachomatis, Mycobacterium tuberculosis, and Salmonella enterica, type I immune responses are elicited through IFNg-producing ILC1s and NK cells. When hosts are exposed to allergens or infected with parasites, ILC2s in the tissues promptly produce type II cytokines including IL-4,5IL-5, IL-13, and amphiregulin and initiate type II immune responses. Extracellular pathogens such as extracellular bacteria and fungi induce type III immune responses through activation of IL-17/IL-22 producing ILC3s. Our lab is trying to elucidate how these ILC subsets are developmentally, functionally, transcriptionally, and epigenetically controlled in the mouse models of diseases and identify therapeutic targets to prevent disease development.

Staff

Professor:
Takashi EBIHARA, M.D., Ph.D.

Associate Professor:
Shunsuke TAKASUGA, Ph.D.
Megumi TATEMATSU, Ph.D.

Research Areas

  1. Roles of mRNA stability in ILC differentiation and function
  2. Trained immunity by ILCs
  3. Activation induced cell death of ILC2s in chronic allergy
  4. Immune checkpoint molecules and ILCs
  5. Long tail effect of PD-1 blockade therapy

Contact Information

Professor: Takashi EBIHARA, M.D., Ph.D.
Tel: +81-18-884-6080
email: tebihara@med.akita-u.ac.jp

Most Recent Achievements

  1. Yamada T, Tatematsu M, Takasuga S, Fuchimukai A, Yamagata K, Seki S, Kuba K, Yoshida H, Taniuchi I, Bernhardt G, Shibuya K, Shibuya A, Yamada T, Ebihara T*. TIGIT mediates activation-induced cell death of ILC2s during chronic airway allergy. J Exp Med. 220(7):e20222005. 2023.
  2. An J, Nagaki Y, Motoyama S, Kuze Y, Hoshizaki M, Kemuriyama K, Yamaguchi T, Ebihara T, Minamiya Y, Suzuki Y, Imai Y, Kuba K. Identification of Galectin-7 as a crucial metastatic enhancer of squamous cell carcinoma associated with immunosuppression. Oncogene. 41(50):5319-5330. 2022.
  3. Miyabe Y, Tomizawa H, Saito H, Yamada T, Shiina K, Koizumi K, Kawasaki Y, Suzuki S, Fukuchi M, Ueki S, Ebihara T, Yamada T. Quantification of Aspergillus fumigatus antigen Asp f 1 in airway tissue and allergic inflammation. Allergy. 77(10):3154-3156. 2022.
  4. Ebihara T*, Tatematsu M, Fuchimukai A, Yamada T, Yamagata K, Takasuga S, Yamada T. Trained innate lymphoid cells in allergic diseases. Allergol Int. (20)30151-9. 2021.
  5. Ebihara T*. Dichotomous Regulation of Acquired Immunity by Innate Lymphoid Cells. Cells. 9(5):1193. 2020.
  6. Ebihara T*, Taniuchi I. Exhausted-like Group 2 Innate Lymphoid Cells in Chronic Allergic Inflammation. Trends Immunol. 40:1095-1104. 2019.
  7. Ardain A, Domingo-Gonzalez R, Das S, Kazer SW, Howard NC, Singh A, Ahmed M, Nhamoyebonde S, Rangel-Moreno J, Ogongo P, Lu L, Ramsuran D, de la Luz Garcia-Hernandez M, Ulland TK, Darby M, Park E, Karim F, Melocchi L, Madansein R, Dullabh KJ, Dunlap M, Marin-Agudelo N, Ebihara T, Ndung'u T, Kaushal D, Pym AS, Kolls JK, Steyn A, Zúñiga J, Horsnell W, Yokoyama WM, Shalek AK, Kløverpris HN, Colonna M, Leslie A, Khader SA. Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis. Nature. 570:528-532. 2019.
  8. Ebihara T* and Taniuchi I. Transcription Factors in the Development and Function of Group 2 Innate Lymphoid Cells. Int J Mol Sci. 20: pii: E1377. 2019.
  9. Miyamoto C, Kojo S, Yamashita M, Moro K, Lacaud G, Shiroguchi K, Taniuchi I, and Ebihara T*. Runx/Cbf complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation. Nat Commun. 10:447. 2019.
  10. Tenno M, Kojo S, Lawir DF, Hess I, Shiroguchi K, Ebihara T, Endo TA, Muroi S, Satoh R, Kawamoto H, Boehm T, Taniuchi I. Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors. J Exp Med. 215:595-610. 2018
  11. Bern MD, Beckman DL, Ebihara T, Taffner SM, Poursine-Laurent J, White JM, Yokoyama WM. Immunoreceptor tyrosine-based inhibitory motif-dependent functions of an MHC class I-specific NK cell receptor. Proc Natl Acad Sci U S A. pii: 201713064. 2017
  12. Ebihara T, Seo W, Taniuchi I. Roles of RUNX Complexes in Immune Cell Development. Adv Exp Med Biol. 962:395-413. 2017.
  13. Azuma M, Takeda Y, Nakajima H, Sugiyama H, Ebihara T, Oshiumi H, Matsumoto M, Seya T. Biphasic function of TLR3 adjuvant on tumor and spleen dendritic cells promotes tumor T cell infiltration and regression in a vaccine therapy. Oncoimmunology. 5:e1188244. 2016.
  14. Ebihara T, Song C, Ryu SH, Plougastel-Douglas B, Yang L, Levanon D, Groner Y, Bern MD, Stappenbeck TS, Colonna M, Egawa T, Yokoyama WM. Runx3 specifies lineage commitment of innate lymphoid cells. Nat Immunol. 16:1124-33, 2015.
  15. Kasamatsu J, Azuma M, Oshiumi H, Morioka Y, Okabe M, Ebihara T, Matsumoto M, Seya T. INAM Plays a Critical Role in IFN-γ Production by NK Cells Interacting with Polyinosinic-Polycytidylic Acid-Stimulated Accessory Cells. J Immunol. 193:5199-207. 2014.
  16. Takaki H, Honda K, Atarashi K, Kobayashi F, Ebihara T, Oshiumi H, Matsumoto M, Shingai M, Seya T. MAVS-dependent IRF3/7 bypass of interferon β-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells. Mol Immunol. 57:100-10. 2014.
  17. Ebihara T, Jonsson AH, and Yokoyama WM. NK Cell Licensing in Mice with Inducible Expression of MHC Class I. Proc Natl Acad Sci U S A. 110:E4232-7. 2013.
  18. Azuma M, Ebihara T, Oshiumi H, Matsumoto M, Seya T. Cross-priming for antitumor CTL induced by soluble Ag + polyI:C depends on the TICAM-1 pathway in mouse CD11c(+)/CD8α(+) dendritic cells. Oncoimmunology. 1:581-592. 2012.
  19. Ebihara T, Azuma M, Oshiumi H, Kasamatsu J, Iwabuchi K, Matsumoto K, Saito H, Taniguchi T, Matsumoto M, Seya T. Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation. J Exp Med. 207:2675-87. 2010.

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