Dale T. Umetsu

Boston Children's Hospital
Karp Laboratories, Rm 10127
1 Blackfan Circle
Boston, MA 02115
Tel: 617 919 2439
Fax: 617 730 0384
Email: dale.umetsu@childrens.harvard.edu

Our laboratory examines immunoregulation at mucosal surfaces, in the lung and in the gut. We focus on CD4+ adaptive T cells (antigen-specific effector and regulatory T cells), and their interactions with innate lymphoid cells (natural killer T (NKT) cells, natural helper cells or nuocytes) and subsets of dendritic cells. We are interested in the cellular, molecular and genetic mechanisms that control immunity, including the interaction of T cells with dendritic cells, and that regulate cytokine synthesis in and the function of CD4+ T cells.

Ongoing studies deal with the examination of:

• the TIM gene family, a family that we discovered in 2001, that regulates the development of Th1/Th2 responses, T cell activation, tolerance and asthma. TIM-1 is the receptor for the hepatitis A virus, and TIM-1, TIM-3 and TIM-4 are all receptors for phosphatidylserine on apoptotic cells. We are studying how these cell surface receptors, and their polymorphic variants shape immunity, viral responses and tolerance.

• the influence of innate immune responses to infection, including influenza A virus, hepatitis A virus,
Listeria monocytogenes and microbiota in the lungs and gut, on adaptive immunity, asthma, tolerance and hepatitis. Innate cells, including innate lymphoid cells (NKT cells and natural helper cells) respond to infectious agents and commensal bacteria through pattern recognition receptors (PRR). The PRR pathways include the conserved/invariant TCR of NKT cells, TIM molecules recognizing apoptotic cells, and the NRLP3 inflammasome in innate cells, and can drive the development of effector and/or regulatory cell responses.

• subsets of CD4+ T cells, TReg cells, invariant NKT cells, natural helper cells and dendritic cells involved in cellular and immunity and in respiratory tolerance. We are studying the role of, and interactions between, these cell types in immunity, and in particular in the development of tolerance, different forms of asthma, and in the regulation of allergy, including food allergy.


1. 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. TIM-1, HAV and the hygiene theory of atopy: Association of TIM-1 with atopy. Nature. 425:576.

2. Stock P, Akbari O, Berry G, Freeman GJ, DeKruyff,RH and DT Umetsu. 2004. Induction of a novel TH1-like regulatory cell that expresses Foxp3 and protects against airway hyperreactivity. Nature Immunol. 5:1149-1156.

3. 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.

4. Chang Y-J, Kim HY, Albacker, Baumgarth N, McKenzie AN, Smith DE, DeKruyff RH and Umetsu DT. 2011. Innate lymphoid cells mediate influenza-induced airway hyperreactivity independent of adaptive immunity. Nature Immunol. 12:631-8. PMID: 21623379.

5. Albacker LA, Chaudhary V, Chang YJ, Kim HY, Chuang YT, Pichavant M, DeKruyff RH, Savage PB, and Umetsu DT. 2013. A fungal glycosphingolipid directly activates natural Killer T cells and rapidly induces airways disease. Nature Medicine, in press.

Last Update: 1/6/2014