Christophe Benoist


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.




We explore how T cells differentiate into their different lineages and final effector states, particularly from the standpoint of self-tolerance and autoimmunity. Studies on autoimmunity explore the molecular and genetic failures of tolerance in diabetes, rheumatoid arthritis and in the disease that appears in Aire-deficient individuals. Major questions tackled are why thymic tolerance is defective in these models, what triggers the autoimmune processes, how their progression is regulated. We ask where and how regulatory “Treg” cells are generated and control autoimmune destruction. Molecular investigations tackle how the Aire transcription factor controls the ectopic expression of self-antigens in the thymus, or how FoxP3 coordinates with other elements in specifying the different facets of the Treg phenotype. Our research involves many collaborations across the campus, and a wide range of technologies are applied to these questions (manipulation of the mouse germline, gene expression profiling, mass spectrometry, RNAi screens). Imaging tools are used to analyze and track autoimmune inflammation in vivo, in mice and human patients. The lab also has an interest in bioinformatic approaches to explore the regulation and connectivity of gene expression at the “Systems Immunology” level. Most of our work involves mouse models, but we also translate some of the leads to human diseases.

References:

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.



Last Update: 1/6/2014