Immunology Faculty Member - Christophe Benoist, MD, PhD

Christophe Benoist, MD, PhD

Harvard Medical School
77 Ave. Louis Pasteur
NRB, 1052G
Boston, MA 02215
Tel: 617- 432-7743
Fax: 617-432-7744
Email: cb@hms.harvard.edu
Visit my lab page here.



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 self-tolerance and orderly responses to obligate commensal microbes. We have found that Treg cells in diverse tissues regulate inflammation in contexts that are not classically immunological, like adipose tissue or muscle injury. Studies on autoimmunity explore the genetics and molecular failures of tolerance in diabetes, rheumatoid arthritis and in 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, and how commensal microbes influence autoimmunity (and more generally immunologic architecture and function). The lab has a long-standing interest in transcriptional regulation, currently asking how Aire controls the ectopic expression of a diverse array of genes in thymic epithelial cells, how FoxP3 and cofactors specify the different facets of the Treg phenotype, or how human genetic variation modifies the T cell transcriptional program. 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 and CyTOF, gene expression analysis, proteomics, in vivo imaging, bioinformatics). The lab often tackles questions at the “Systems Immunology” level, and partakes in the Immunological Genome Project.



Last Update: 8/15/2014



Publications

1. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine A, Benoist C, Shoelson SE and Mathis D. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009; 15:930-939.

2. Feuerer M, Shen Y, Littman D, Benoist C and Mathis D. How punctual ablation of Foxp3+ T cells unleashes an autoimmune lesion within the pancreatic islets. Immunity 2009; 31:654-656..

3. Abramson J, Giraud M, Benoist C and Mathis D. Aire's partners in the molecular control of immunological tolerance. Cell 2010; 140:123-135.

4. Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C and Mathis D. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 2010; 32:815-27.

5. D'Alise AM, Ergun A, Hill JA, Mathis D, Benoist C. A cluster of coregulated genes determines TGF-{beta}-induced regulatory T-cell (Treg) dysfunction in NOD mice. Proc Natl Acad Sci U S A. 2011; 108:8737.



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