Christophe O. Benoist
The CBDM lab has varied interests, generally organized around the genomic control of immunological tolerance and autoimmune diseases in T lymphocytes. We study how T cells differentiate into different lineages in the thymus, and how the Aire transcription factor promotes ectopic gene expression to expose thymocytes to tissue-specific antigens. With regards to peripheral tolerance, we have a broad interest in regulatory Treg cells, their mode of action in ensuring tolerance to self and to commensal microbes, and their deleterious impact on tumor immunity. We have found that tissue-resident Treg cells in diverse organs regulate inflammation in non-immunological contexts, like adipose tissue or muscle injury.
Studies on autoimmunity explore the genetics and molecular failures of tolerance in diabetes or rheumatoid arthritis and Aire-deficiency (APECED) or FoxP3 deficiency (IPEX), and have been interested in how human genetic variation modifies T cell activation and tolerance. Major questions tackled are why thymic tolerance is defective in these models, what triggers the autoimmune processes, how their progression is regulated. More recently, we have studied the influence of commensal microbes on the immune system and autoimmune diseases, and discovered a very intriguing multi-generational transmission of Treg/IgA traits. We are also pursuing unexpected observations showing that microbe/immune interactions recruit the nervous system in a triangular cross-talk.
The lab has a long-standing interest in transcriptional regulation and transcription factors. An ever-fascinating puzzle is how Aire controls the ectopic expression of a wide array of genes in the thymus. We tackle how FoxP3 specifies the different facets of Treg cells, how it connects to enhancer-promoter DNA loops, and how its mysterious disorganized domain interacts with various cofactors to mold the Treg signature. The lab has traditionally been an early-adopter of cutting edge technologies, most recently CRISPR mutagenesis in vivo or single-cell genomics. The lab often tackles questions at the “Systems Immunology” level, and plays a leadership role in the Immunological Genome Project (ImmGen). Through these collaborations, we have developed significant skills in computational biology, and are excited by the application of Artificial Intelligence tools to chart the complexities of genomic or immunological networks.
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