Our work investigates immune regulation and inflammation. Using mice as models of human diseases, we use methods that span the scientific disciplines and include physiology, cellular immunology, pharmacology and molecular biology. Our primary interest is in determining what leads to sensitization towards antigens and drives allergic responses using models of asthma, eczema and food allergy. Recent work has focused onto two areas:
1) Histamine and Histamine Receptors in Immune Sensitization
Histamine is a small vasoactive mediator that is released from cells involved in the immediate allergic responses to antigen exposure, such as mast cells in the skin or lung. Antihistamine drugs are commonly used for treating allergic diseases of the upper airways but have not found their way into use for other allergic conditions. Our work showed that antihistamines directed against the type-1 receptor actually prevented the development of asthma in mice by affecting how the antigen specific T lymphocytes developed. Using other mice, that specifically lacked the type 1 histamine receptor, we went on to discover that this receptor is essential for how the T lymphocytes move into tissues upon antigen exposure.
Studies have shown that antihistamines against the type-2 histamine receptor actually promote food allergy. We are investigating the mechanisms through which this occurs. We are investigating whither exposure to type-2 histamine receptor targeted drugs, which are commonly used for gastric reflux diseases, may alter the immune system and leave individuals susceptible to developing allergies.
2) IgE and Mast Cells in Vaccination via the Skin
The World Health Organization and UNICEF have stated that the need to improve injection safety for vaccination is of major importance. One solution to this problem is vaccination via the skin. However, to generate good immune responses via this route, additional “stimulatory” agents are needed. These are usually of bacterial origin and not yet licensed by the FDA. Our work has shown that IgE (the antibody involved in allergies) and mast cells, the cell IgE binds to, actually help to promote sensitization to antigens. In allergy, this leads to “allergic spread” whereby an allergic individual is more likely to become allergic to other antigens. In vaccination via the skin, altering these responses may promote immune protection.
Publications:
Bryce PJ & Oettgen HC. Antigen Independent Effects of IgE. Curr Allergy Asthma Rep. 2005 May;5(3):186-190.
Bryce PJ, Miller ML, Miyajima I, Tsai M, Galli SJ, Oettgen HC. Immune sensitization in the skin is enhanced by antigen-independent effects of IgE. Immunity. 2004 Apr;20(4):381-92.
Gurish MF, Bryce PJ, Tao H, Kisselgof AB, Thornton EM, Miller HR, Friend DS, Oettgen HC. IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis. J Immunol. 2004 ;172:1139-45.
Castigli E, Scott S, Dedeoglu F, Bryce P, Jabara H, Bhan AK, Mizoguchi E, Geha RS. Impaired IgA class switching in APRIL-deficient mice. P.N.A.S. 2004 ;101:3903-8.
Alonzi T, Newton IP, Bryce PJ, Di Carlo E, Lattanzio G, Tripodi M, Musiani P, Poli V. Induced somatic inactivation of STAT3 in mice triggers the development of a fulminant form of enterocolitis. Cytokine. 2004 ;26:45-56.
Kawamoto S, Yalcindag A, Laouini D, Brodeur S, Bryce P, Lu B, Humbles AA, Oettgen H, Gerard C, Geha RS. The anaphylatoxin C3a downregulates the Th2 response to epicutaneously introduced antigen. J Clin Invest. 2004 Aug;114(3):399-407.
