Dale T. Umetsu
Division of Immunology
Department of Pediatrics
Karp Research Building, 10th Floor
Children's Hospital
One Blackfan Circle
Boston, MA 02115
Tel: 617-919-2439
Fax: 617-730-0384
email: dale.umetsu@childrens.harvard.
Our laboratory focuses on the study of subpopulations of human and murine CD4+ T cells, which play a central role in the regulation of adaptive immunity and tolerance. We study allergic diseases and asthma in humans and in mice as models of immune dysregulation, and examine the function of CD4+ αß TCR T cells with restricted cytokine profiles (Th1, Th2 and Th0 cells), CD4+ antigen-specific regulatory T cells (TReg), as well as iNKT cells in regulating these diseases. We are interested in the cellular, molecular and genetic mechanisms that control the interaction of T cells with dendritic cells, and that regulate cytokine synthesis in and the function of CD4+ T cells, which mediate development of, or protection against, disease.
Ongoing studies deal with the examination of:
- the cellular and molecular mechanisms that drive polarization of cytokine synthesis in memory and naive populations of CD4+ T cells.
- subsets of CD4+ T cells, TReg cells, iNKT cells and dendritic cells involved in cellular and humoral immunity and in respiratory tolerance induction.
- the TIM gene family, a family that we recently discovered, that regulates the development of Th1/Th2 responses, T cell activation, tolerance and asthma.
- the influence of innate immunity to infection with influenza A virus, hepatitis A virus and Listeria monocytogenes on adaptive immunity, asthma and tolerance.
References:
- Akbari O, DeKruyff RH, Umetsu DT. 2001. Pulmonary dendritic cells secreting IL-10 mediate T cell tolerance induced by respiratory exposure to antigen. Nature Immunology. 2:725-31.
- McIntire JJ, Umetsu SE, Omid Akbari, Potter M, Kuchroo V, Barsh GS, Freeman GJ, Umetsu DT, DeKruyff RH. 2001. Identification of Tapr, an airway hyperreactivity regulatory locus, and the associated Tim Gene Family. Nature Immunology. 2:1109-16.
- Umetsu DT, McIntire JJ, Macaubas C, Akbari O, DeKruyff RH. 2002. Asthma: an epidemic of dysregulated immunity. Nature Immunology. 3:715-720.
- Akbari O, Freeman GJ, Meyer EH, Greenfield EA, Chang TT, Sharpe AH, Berry G, DeKruyff RH and Umetsu DT. 2002. Antigen-specific regulatory T cells develop via the ICOS-ICOS-Ligand pathway and inhibit allergen-induced airway hyperreactivity. Nature Medicine. 8:1024-32.
- Akbari O, Stock P, Meyer E, Kronenberg M, Sidobre S, Nakayama T, Taniguchi M, Grusby MJ, DeKruyff RH, and Umetsu DT. 2003. Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen induced airway hyperreactivity. Nature Medicine. 9:582-88.
- McIntire JJ, Umetsu SE, Macaubas C, Hoyte EG, Cinnioglu C, Cavalli-Sforza LL, Barsh GS, Hallmayer JF, Underhill PA, Risch NJ, Freeman GJ, DeKruyff RH, Umetsu DT. 2003. Hepatitis A virus link to atopic disease: Association of TIM-1 with atopy. Nature. 425:576.
- Stock P, Akbari O, Berry G, Freeman GJ, DeKruyff,RH and Umetsu DT. 2004. Induction of TH1-like regulatory cells that express Foxp3 and protect against airway hyperreactivity. Nature Immunol. 5:1149-1156.
- Umetsu SE, Lee W-L, McIntire JJ, Downey L, Sanjanwala B, Akbari O, Berry GJ, Nagumo H, Freeman GJ, Umetsu DT, DeKruyff RH. 2005. TIM-1 induces T cell activation and inhibits the development of peripheral tolerance. Nature Immunol. 6:447-54.
- Meyer EH, Goya S, Akbari O, Berry GJ, Savage PB, Kronenberg M, Nakayama T, DeKruyff RH and Umetsu DT. 2006. Glycolipid mediated activation of iNKT cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T cells. Proc Natl Acad Sci. 103:2782-2787.
- Akbari O, Faul JL, Hoyte EG, Berry GJ, Wahlström J, Kronenberg M, DeKruyff RH, and Umetsu DT. 2006. Pulmonary CD4+, invariant T cell receptor+ NKT cells in bronchial asthma. New Engl J Med. 354:1117-29.
Immunology webpage updated 12/02/2009