Hideki Ueno, M.D., Ph.D. Professor
The immune system plays a central role to protect our body from the invasion of pathogens. It is important to note, however, that the immune system requires to be strictly controlled, because both insufficient and excessive immune response causes health issues. The cellular networks, composed of various types of immune cells as well as non-immune cells such as epithelial cells and endothelial cells, maintain the homeostasis of the immune system in a steady state, and induce the optimal type and the magnitude of immune responses according to the nature of invading pathogens. Our laboratory studies the human immune system, with a particular focus on the adaptive immune system. Our interest is to determine the cellular and molecular mechanisms by which the adaptive immune system is controlled in humans, and establish the link between the dysregulation of the adaptive immune system and human diseases.
Research and EducationRecent years have witnessed the development of a number of new treatments for human diseases targeting the molecules expressed by the immune cells. Now we know that the immune system plays a key pathogenic role in a much broader range of diseases than previously anticipated. Thus, the research on the immune system, both basic and clinical, will become even more important than the past for the generation of new treatments. Studies of the immune system in animal models have been invaluable and will remain the mainstay in the immunology research. On the other hand, the translatability of the findings in animal models to humans has always been an issue, and our laboratory also has identified many differences in the regulation of antibody responses between humans and mice.
Our laboratory performs immunology research on human samples derived from healthy subjects and patients. The research topic includes the basic science of human immune cells; determination of the mechanisms controlling the adaptive immune responses in humans; and identification of the cellular and molecular alterations in the immune cells associated with human diseases. We are particularly interested in tumor immunology, autoimmune diseases, allergy, and neuroinflammatory diseases. By using state-of-the-art equipment and technologies, we aim to perform the next generation of human immunology research and contribute to the development of new treatments for human diseases with unmet medical needs.
The regulation of human CD4+ T cell differentiation by cytokines. We have reported that the three cytokines, IL-12, IL-23, TGF-b, play a fundamental role to determine the fate of CD4+ T cell differentiation in humans.
Two positive feed-forward loops by the Immune complexes containing nuclear components in human systemic lupus erythematosus. Both plasmacytoid DCs and conventional DCs/macrophages contribute to the feed-forward loops.
- Schmitt N, Morita R, Bourdery L, Bentebibel SE, Zurawski SM, Banchereau J, Ueno H. Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12. Immunity. 2009;31(1):158-69.
- Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity. 2011;34(1):108-21.
- Bentebibel SE, Lopez S, Obermoser G, Schmitt N, Mueller C, Harrod C, Flano E, Mejias A, Albrecht RA, Blankenship D, Xu H, Pascual V, Banchereau J, Garcia-Sastre A, Palucka AK, Ramilo O, Ueno H. Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination. Sci Transl Med. 2013;5(176):176ra32.
- Schmitt N, Liu Y, Bentebibel SE, Munagala I, Bourdery L, Venuprasad K, Banchereau J, Ueno H. The cytokine TGF-beta co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells. Nat Immunol. 2014;15(9):856-65.
- Jacquemin C, Schmitt N, Contin-Bordes C, Liu Y, Narayanan P, Seneschal J, Maurouard T, Dougall D, Davizon ES, Dumortier H, Douchet I, Raffray L, Richez C, Lazaro E, Duffau P, Truchetet ME, Khoryati L, Mercie P, Couzi L, Merville P, Schaeverbeke T, Viallard JF, Pellegrin JL, Moreau JF, Muller S, Zurawski S, Coffman RL, Pascual V, Ueno H*, Blanco P*. OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response. Immunity. 2015;42(6):1159-70. * Equal contributors.
Immunology and Cell BiologyProfessor: Hideki Ueno
Associate Professor: Hiroyuki Yoshitomi