Abstract: Series 107, Lecture 3

The Harvey Lectures Series 107 (2011—2012)

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Lecture #3: Thursday, January 19, 2012 — Time and Location

The Commensal Microbiota as the Fulcrum for a Balanced Immune System

Dan R Littman, MD, PhD

Dan R Littman, MD, PhD

Helen L and Martin S Kimmel Professor of Molecular Immunology and
Professor of Pathology and Microbiology
Investigator, Howard Hughes Medical Institute
Skirball Institute of Biomolecular Medicine

Howard Hughes Medical Institute, New York University School of Medicine

New York, New York

Dr Littman's Website

The constituents of the commensal microbiota that inhabit our intestine have co-evolved with us for mutual benefit. They regulate maturation of gut lymphoid tissues and the balance of pro- and anti-inflammatory intestinal lymphocytes. Lymphocytes that produce the cytokines IL-17 and IL-22 protect mucosal surfaces from damage inflicted by bacteria and fungi, but also have critical roles in multiple autoimmune diseases and in inflammatory processes that impact diseases ranging from asthma to atherosclerosis and cancer. Most prominent among these lymphocytes are the Th17 cells, a subset of CD4+ T-helper cells that mediate autoimmunity in mice and humans. Disruption of the balance between Th17 and anti-inflammatory regulatory T cells, which is governed by signals from distinct commensal microbes, can predispose to autoimmune diseases that affect distal organs. Inflammatory lymphoid cells share a genetic program dependent on expression of the orphan nuclear receptor RORγt, a promising target for anti-inflammatory therapy. A genomic analysis of the Th17 cell transcriptional regulatory network is being used to identify additional key factors required for Th17-mediated inflammation and to uncover new therapeutic targets in autoimmune disease.