Biosketch / Results /
Juan LafailleProfessor, Department of Pathology
Professor, Department of Medicine
Research SummaryAlthough most normal immune responses against pathogens require the action of T-lymphocytes, their improper control lies at the heart of two types of disease: autoimmunity and allergy. Our laboratory uses transgenic and knockout mice to study the molecular mechanisms responsible for the normal control of T-lymphocyte reactivity and the changes that occur when T-lymphocytes become either aggressive against self antigens or inappropriately reactive against substances (allergens) normally present in the environment.
Currently, we are examining the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, in transgenic mice bearing antimyelin basic protein (MBP) T-lymphocytes. Mice harboring large numbers of anti-MBP T-lymphocytes in addition to other lymphocytes seldom develop EAE spontaneously. However, when these mice are crossed with RAG-l KO mice, thereby producing only anti-MBP T-lymphocytes, they all develop spontaneous EAE. The sharp contrast in susceptibility to EAE between the two types of anti-MBP transgenic mice, one carrying regulatory lymphocytes and the other not, enables us to pursue identifying and characterizating those cells. We also focus on a transgenic mouse model for asthma to determine in vivo the factors controlling the synthesis of important interleukins involved in the asthmatic process such as IL-4 and IL-5 and the increased production of immunoglobulin E.
Research InterestsMolecular Pathogenesis of Autoimmune and Allergic Diseases
Increased generation of Foxp3(+) regulatory T cells by manipulating antigen presentation in the thymus
Lin, Jiqiang; Yang, Lu; Silva, Hernandez Moura; Trzeciak, Alissa; Choi, Yongwon; Schwab, Susan R; Dustin, Michael L; Lafaille, Juan J. Increased generation of Foxp3(+) regulatory T cells by manipulating antigen presentation in the thymus. Nature communications. 2016 Feb 29;7:10562-10562 (2006242)
Biology of IgE production: IgE cell differentiation and the memory of IgE responses
He, Jin-Shu; Narayanan, Sriram; Subramaniam, Sharrada; Ho, Wen Qi; Lafaille, Juan J; Curotto de Lafaille, Maria A. Biology of IgE production: IgE cell differentiation and the memory of IgE responses. Current topics in microbiology & immunology. 2015 ;388:1-19 (1486802)
Inhibition of Gli1 mobilizes endogenous neural stem cells for remyelination
Samanta, Jayshree; Grund, Ethan M; Silva, Hernandez M; Lafaille, Juan J; Fishell, Gord; Salzer, James L. Inhibition of Gli1 mobilizes endogenous neural stem cells for remyelination. Nature. 2015 Sep 30;526(7573):448-452 (1789792)
Massive monoclonal expansion of functionally stable human regulatory T cells
Nowatzky, J; Manches, O; Bhardwaj, N; Lafaille, J. Massive monoclonal expansion of functionally stable human regulatory T cells [Meeting Abstract]. Journal of immunology (1950). 2014 01 May;192(1):?-? (1058252)
Focused specificity of intestinal T17 cells towards commensal bacterial antigens
Yang, Yi; Torchinsky, Miriam B; Gobert, Michael; Xiong, Huizhong; Xu, Mo; Linehan, Jonathan L; Alonzo, Francis; Ng, Charles; Chen, Alessandra; Lin, Xiyao; Sczesnak, Andrew; Liao, Jia-Jun; Torres, Victor J; Jenkins, Marc K; Lafaille, Juan J; Littman, Dan R. Focused specificity of intestinal T17 cells towards commensal bacterial antigens. Nature. 2014 Apr 13;510(7503):152-156 (963022)