- Professor, Department of Pathology, Cancer Research Center, Committee on Immunology
M.D., University of Paris VI, Paris, 1985
Ph.D., University of Paris VI, Paris, 1992
The University of Chicago
929 East 57th Street
Chicago, Illinois 60637
Phone: (773) 834-8646
Innate and Innate-like Lymphocytes in Immunity and Homeostasis
Unlike conventional T and B cells of adaptive immunity, innate-like B and T cell lineages acquire effector differentiation and tissue residency properties during development, following exposure to endogenous rather than foreign ligands. In that respect, they closely resemble Innate Lymphoid Cells (ILC) and together they represent a substantial fraction of total lymphocytes in tissues and at mucosal barriers, carrying out first-line defense and promoting recruitment of subsequent adaptive immunity. Studies in our laboratory aim at understanding their identity, development and role in health and disease.
Our early studies focused on NKT cells, a prominent population of innate-like T lymphocytes in mouse and human that are characterized by the expression of semi-invariant TCRs with specificity for microbial and self lipids presented by the CD1 family of MHC I like molecules. These studies led to the identification of the signature transcription factor Promyelocytic Leukemia Zinc Finger (PLZF) encoded by Zbtb16, which is necessary and sufficient for acquisition of the NKT cell effector program in the thymus. By generating PLZF-reporter mice, we discovered that PLZF expression during development was a signature feature not only for NKT cells, but also for most innate and innate-like lymphocyte lineages. For example, a high level of PLZF expression identified the common precursor to ILC. Furthermore, by performing PLZF ChIP-seq analysis we identified the targets of PLZF and defined the genetic architecture of the innate lymphoid effector program.
More recently, we have initiated studies of other lineages of innate-like lymphocytes. By cloning and transgenically expressing TCRs of innate-like intestinal intraepithelial lymphocytes, we have characterized their unusual specificity and developmental pathway in vivo. Likewise, by cloning and transgenically expressing B cell receptors of intestinal lamina propria B cells, we are defining the development and specificity of IgA secreting B cells and their role in microbiota homeostasis
Collectively, our studies define the identity, the development and the functional contribution of the myriad lineages that populate tissues and mucosal barriers in the steady state. They generate knowledge of critical molecular components, for example transcription factors, that define these lineages and allow the generation of reporter mice where these lineages can be easily identified and manipulated in vivo to explore their roles in homeostasis and in various disease conditions.