Christophe Benoist

Our lab has several interests, generally organized around the genetic and genomic control of immunological tolerance and autoimmune diseases. 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 Treg cells in diverse tissues regulate inflammation in extra-immunological contexts, like adipose tissue or muscle injury.

Studies on autoimmunity explore the genetics and molecular failures of tolerance in diabetes, rheumatoid arthritis and Aire-deficiency (APECED) or FoxP3 deficiency (IPEX). 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 been interested in the influence of commensal microbes on the immune system and autoimmune diseases, with unexpected crosstalk from the nervous system.

The lab has a long-standing interest in transcriptional regulation, currently asking how Aire controls ectopic gene expression of a diverse array of genes, how FoxP3 and cofactors specify the different facets of Treg cells, or how human genetic variation modifies the T cell transcriptional program. We ask how transcriptional promoters and enhancers are controlled by the organization of DNA in chromatin and nuclear loops. Our research involves many collaborations across Boston and elsewhere, and a wide range of technologies are applied (conventional and CRISPR-based mouse germline manipulation, flow cytometry, gene expression analysis, proteomics, in vivo imaging, bioinformatics). The lab often tackles questions at the “Systems Immunology” level, and we are active participants in the Immunological Genome Project, and have jumped into the fascinating perspectives offered by single-cell transcriptomics.