时间：2023年11月6日（周一）上午9:00-10:30

Time：9:00-10:30 AM, Monday, November 6, 2023

地点：西湖大学云谷校区E10-201教室

Venue: E10-201, Yungu Campus

主持人：中国科学院院士  董晨

Host: Chen DONG, Academician, Chinese Academy of Sciences 

主讲人/Speaker：

Dr. MARK M. DAVIS

Investigator, Howard Hughes Medical Institute

Professor, Department of Microbiology and Immunology

Director, Institute for Immunity, Transplantation and Infection，Stanford University School of Medicine Stanford, California

报告题目/Title:

Immune Organoids and Combinations to Advance Our Understanding of Autoimmunity, Vaccination and Infection

讲座摘要/Abstract:

It is increasingly clear that Kir+CD8+ T cells in humans and Ly49+ CD8+ T cells in mice are a major axis of T cell tolerance, operating in parallel to CD4+ regulatory cells (Li et al., Science 2022). They are particularly active during infections, presumably to control self-reactive T cells, whereas CD4+ regulatory cells seem quiescent during active COVID-19 or Influenza infections. Consistent with this proposed function, a conditional knockout of Ly49+ CD8+’s results in clear signs of autoimmunity in mice infected with either LCMV or influenza (Li et al., Science 2022). To explore this further, we have taken advantage of our recently developed immune organoid methodology using human tonsils or spleens (Wagar et al., Nature Medicine 2021) which reproduce key features of adaptive immunity in vitro. The malleability of this system, especially with the ability to perform gene editing using CRISPR-Cas9, is allowing us to test specific hypotheses and create models of autoimmunity in an entirely human system. Here we have asked what the division of labor is between CD4+ and CD8+ regulatory T cells.  Since FoxP3 is a key driver of CD4+ T reg function in CD4+ but not CD8+ regulatory cells T cells, we KO’d that gene in tonsil T cells and found that now the B cells can express self reactive antibodies, whereas disabling CD8+ regulatory cells has only a minor effect this type of autoreactivity, but a unique effect on autoreactive CD4+ T cells. Thus we can use these organoids gene editing and other manipulations to rapidly investigate important mechanisms and interactions in human immunity. We have also recently worked with human spleens from organ donors, and this allows us to study interactions between an immune organ and tissues such as the lung or skin that interact with a lymphoid organ. This gives us an entirely new way to study the human immune response to infection and vaccination.

讲座联系人/Contact:

科技合作部Sci-tech02@westlake.edu.cn