Title of Presentation

“Exploring Immunosenescence: Paving the Way for Heathy Aging”

The immune system normally eliminates pathogens and cancer cells. With age, its function gradually declines, which raises the risk that an infection could become serious or a cancer could develop. At the same time, the risk of some other immune responses, such as inflammation and autoimmunity, increases, potentially resulting in the development of a range of age-related diseases. This phenomenon of immunosenescence, with its two sides that appear to conflict with one another, can be a common underlying factor behind different diseases that increase with age. What it really is, or what causes it to happen, remains largely unknown, however.

T cells are immune cells that play a central role in the adaptive immune response. They regulate the functions of antibody-producing B cells as well as phagocytes, while directly killing cancerous or virus-infected cells. In spite of such critical roles they play, the thymus, the organ that produces and matures T cells, reaches its peak in early childhood and gradually decreases in size as the fat that surrounds it increases (i.e., thymus involution). By the time one is in their 20s, the number of T cells newly produced declines to below one-tenth of that in neonatal life. This means that T cells need to be maintained in the body for a long period of time, which makes them the immune cells that are most susceptible to the effect of aging.

In our research, my colleagues and I aim to gain better understanding of how thymus development and involution occurs, and how the fact that the T cell production declines at a relatively early age in life could be related to a range of diseases that increase with age, as well as to develop technologies to prevent or intervene against such diseases. It is also important to identify what causes substantial differences observed among individuals in the course and degree of the aging, even though its development takes a largely similar time course in a majority of people. In this presentation, I will discuss these points with reference to a study we recently conducted, which compared SARS-CoV-2 reactive T cells in young people in their 20s to those in elderly people in their 70s.

Human life expectancy is expected to increase further. Some estimate that young people who are in their 20s today may on average live to the age of 100 years or older. This means that we will need to maintain our T cells in good condition for an even longer period following thymus involution. Understanding immune characteristics of the elderly, whose population is set to continue expanding further, and providing healthcare that is appropriate for them, are urgent issues facing modern medicine in our effort to achieve a healthy aging society.

 

Profile

Web Site URL

http://www.cira.kyoto-u.ac.jp/hmy/

A brief Biography(As of August 1, 2021)

Mar 1995	BS Faculty of Applied Biological Sciences, Hiroshima University
Mar 1997	MS Division of Hematology, Institute of Clinical Medicine, University of Tsukuba
Apr 1997	Pharmaceutical Division, Clinical Development Department, KIRIN Brewery Company, Limited.
Apr 1999	Graduate School of Medicine, Kyoto University
Apr 2002	Research Fellow, The Japan Society for the Promotion of Science (DC2)
Mar 2003	Ph.D. Department of Cell Biology, Graduate School of Medicine, Kyoto University (supervised by Dr. Shoichiro Tsukita)
Apr 2003	Assistant Professor, Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University (supervised by Dr. Nagahiro Minato)
Dec 2010	Associate Professor, Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University
May 2017-Present	Professor, Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University
Jul 2017-Present	Professor, Immunobiology, Graduate School of Medicine, Kyoto University

Details of selected Awards and Honors

2010	62nd Best Young Scientist Award, Japan Society for Cell Biology
2011	3rd Kyoto University Tachibana Award for Outstanding Women Researchers
2012	Young Scientist Award from the Ministry of Education, Culture, Sport, Science and Technology, Japan
2017	Kao Science Award

A list of selected Publications

Hamazaki Y, Fujita H, Kobayashi T, Choi Y, Scott HS, Matsumoto M, Minato N.　Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin. Nat. Immunol. 2007 Mar; 8(3):304-11.

Shimatani K, Nakashima Y, Hattori M, Hamazaki Y, Minato N. PD-1⁺ memory phenotype CD4⁺ T cells expressing C/EBPα underlie T cell immunodepression in senescence and leukemia. Proc Natl Acad Sci USA 2009 Sep 15;106:15807-12.

Kawai Y*, Hamazaki Y*⁺, Fujita H, Fujita A, Sato T, Furuse M, Fujimoto T, Jetten AM, Agata Y and Minato N. Claudin-4 induction by E protein activity in later stages of CD4/8 double-positive thymocytes to increase positive selection efficiency. Proc Natl Acad Sci USA 2011 Mar 8;108(10):4075-80.

Sekai M, Hamazaki Y^✝, Minato N. Medullary thymic epithelial stem cells maintain a functional thymus 4to ensure lifelong central T cell tolerance. Immunity. 2014 Nov 14: 41(5), 753–761.

Tahir S, Fukushima Y, Sakamoto K, Sato K, Fujita H, Inoue J, Uede T, Hamazaki Y, Hattori M, Minato N. A CD153+CD4+ T Follicular Cell Population with Cell-Senescence Features Plays a Crucial Role in Lupus Pathogenesis via Osteopontin Production. J Immunol. 2015 Jun 15;194(12):5725-35.

Hamazaki Y^✝. Adult thymic epithelial cell (TEC) progenitors and TEC stem cells – Models and mechanisms for the development and maintenance of thymic epithelial cells. Eur J Immunol. 2015 Nov;45(11):2985-93.

Hamazaki Y^✝, Sekai M, Minato N. Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution. Immunol Rev. 2016 May;271(1):38-55. (Invited review)

Sato K, Kato A, Sekai M, Hamazaki Y, Minato N. Physiologic Thymic Involution Underlies Age-Dependent Accumulation of Senescence-Associated CD4⁺ T Cells. J Immunol. 2017 Jul 1;199(1):138-148.

Kato A, Takaori-Kondo A, Minato N, Hamazaki Y^✝. CXCR3^high CD8⁺ T cells with naïve phenotype and high capacity for IFN-γ production are generated during homeostatic T-cell proliferation. Eur J Immunol. 2018 Oct;48(10):1663-1678.

Minato N, Hattori M, Hamazaki Y. Physiology and Pathology of T-cell Aging. Int Immunol. 2020 Apr 12;32(4):223-231.

Jo N, Zhang R, Ueno H, Yamamoto T, Weiskopf D, Nagao M, Yamanaka S and Hamazaki Y^✝. Aging and CMV Infection Affect Pre-existing SARS-CoV-2-Reactive CD8+ T Cells in Unexposed Individuals. Front. Aging 2021 Aug 10;2:719342.