Dan Littman (NYU / HHMI) 2: Shaping of Immune Responses by the Microbiota

https://www.ibiology.org/immunology/th17

Th17 cells are important in our protective immune response to bacteria and fungi. They also can exist, however, in a pathogenic form that causes autoimmune disease.

In his first lecture, Dan Littman discusses the opposing roles of Th17 cells. They protect mucosal surfaces from infection with bacteria and fungi, but they can also cause autoimmune inflammation. Using a mouse model of autoimmunity called experimental autoimmune encephalitis (EAE), Littman and his lab have shown that there are two types of Th17 cells. Non-pathogenic Th17 cells are induced by the microbiota and protect barrier surfaces, while pathogenic Th17 cells are induced by the presence of IL-23, likely the result of inflammation elsewhere in the body. Both types Th17 cells secrete the cytokines IL-17A, IL-17F and IL-22, however, pathogenic Th17 cells also secrete interferon gamma (IFNγ) which induces further inflammation and autoimmune disease. In the last 10 years, several classes of innate lymphoid cells have been found to share similar cytokine profiles to Th17 cells and these cells appear to be another important layer in protecting surfaces in the gut and lung from infection.

In his second talk, Littman explains that different commensal microbes in our gut elicit different T cell responses - either pathogenic or non-pathogenic. His lab is beginning to identify the pathogens and decipher the pathways that determines the host T cell response. This research has important clinical relevance since a cancer patient’s microbiota may help determine their response to chemotherapy. Microbiota that induce non-pathogenic Th17 cells are protective against autoimmunity but may decrease anti-tumor immunity, while microbiota that contribute to autoimmunity may enhance anti-tumor T cell responses.

Speaker Biography:
Dan Littman is the Helen and Martin Kimmel Professor of Molecular Immunology in the Department of Pathology and a professor in the Department of Microbiology at the Skirball Institute of Biomolecular Medicine of New York University School of Medicine. He is also an Investigator of the Howard Hughes Medical Institute.

Littman discovered the excitement of science while he was an undergraduate student at Princeton University. He went on to receive his M.D. and Ph.D. from Washington University in St. Louis. As post-doc in Richard Axel’s lab at Columbia University, Littman isolated the genes for CD8 and CD4, molecules involved in T lymphocyte development. Littman then joined the faculty of the University of California, San Francisco where he was one of the first scientists to recognize that HIV infects T helper cells by binding to CD4. Since 1995, Littman has been based at NYU.

Littman’s lab has continued to study the development and differentiation of T lymphocytes. They are interested in understanding how a normal protective immune response differs from a pathogenic response such as that found in inflammation and autoimmune disease. Currently, they are also investigating the importance of the microbiome in influencing immunity.

Littman is a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Science and the American Academy of Microbiology. His groundbreaking work has been recognized with many prizes including the 2004 New York City Mayor’s Award for Excellence in Science and Technology, the 2013 Ross Prize in Molecular Medicine, and the 2016 Vilcek Prize in Biomedical Science amongst others. Learn more about Littman’s research here:
https://med.nyu.edu/skirball-lab/littmanlab/Home.html

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