Toshihiro Ito, Ph.D.
Steven Kunkel, Ph.D.
Granulomas represent a spectrum of inflammatory sequestration responses that may be initiated by a variety of agents, including noninfectious environmental factors and infectious microbial pathogens; however, the mechanism of granuloma formation is still unclear. Recent data have indicated that the controlled expression of Notch receptor proteins on Th cells is essential for normal T cell development and maturation. My goal is to clarify the role of Notch system towards Th cell differentiation using our well-studied models of polarized Th1/Th2 cell-mediated anamnestic pulmonary granulomatous inflammation.
Ito T , Schaller M, Hogaboam CM, Standiford TJ, Sandor M, Lukacs NW, Chensue SW, Kunkel SL. 2009. TLR9 regulates the mycobacteria-elicited pulmonary granulomatous immune response in mice through DC-derived Notch ligand delta-like 4. J Clin Invest . 2009 119:33-46.
Ramaprakash H, Ito T , Standiford TJ, Kunkel SL, Hogaboam CM. 2009. Toll-like receptor 9 modulates immune responses to Aspergillus fumigatus conidia in immunodeficient and allergic mice. Infect Immun . 77:108-19.
Ishii M, Hogaboam CM, Joshi A, Ito T , Fong DJ, Kunkel SL. 2008. CC chemokine receptor 4 modulates Toll-like receptor 9-mediated innate immunity and signaling. Eur J Immunol . 38:2290-302.
Suzaki Y, Hamada K, Nomi T, Ito T , Sho M, Kai Y, Nakajima Y, Kimura H. 2008. A small-molecule compound targeting CCR5 and CXCR3 prevents airway hyperresponsiveness and inflammation. Eur Respir J . 31:783-9.
Ito T , Schaller M, Hogaboam CM, Standiford TJ, Chensue SW, Kunkel SL. 2007. TLR9 activation is a key event for the maintenance of a mycobacterial antigen-elicited pulmonary granulomatous response. Eur J Immunol . 37:2847-55.
Hamada K, Suzaki Y, Leme A, Ito T , Miyamoto K, Kobzik L, Kimura H. 2007. Exposure of pregnant mice to an air pollutant aerosol increases asthma susceptibility in offspring. J Toxicol Environ Health A . 70:688-95.
Ito T , Hamada K, Suzaki Y, Matsui N, Kita E, Kimura H. 2005. Subcutaneous vaccination of Mycobacterium bovis Bacillus Calmette-Guérin attenuates allergic inflammation in a murine model of asthma. Allergology International. 4: 601-609
Suzaki Y, Hamada K, Sho M, Ito T , Miyamoto K, Akashi S, Kashizuka H, Ikeda N, Nakajima Y, Iwase M, Homma I, Kobzik L, Kimura H. 2005. A potent antiangiogenic factor, endostatin prevents the development of asthma in a murine model. J Allergy Clin Immunol . 116:1220-7.
Akadegawa K, Ishikawa S, Sato T, Suzuki J, Yurino H, Kitabatake M, Ito T , Kuriyama T, Matsushima K. 2005. Breakdown of mucosal immunity in the gut and resultant systemic sensitization by oral antigens in a murine model for systemic lupus erythematosus. J Immunol . 174:5499-506.
Sato T, Ishikawa S, Akadegawa K, Ito T , Yurino H, Kitabatake M, Yoneyama H, Matsushima K. 2004. Aberrant B1 cell migration into the thymus results in activation of CD4 T cells through its potent antigen-presenting activity in the development of murine lupus. Eur J Immunol . 34:3346-58.
Yurino H, Ishikawa S, Sato T, Akadegawa K, Ito T , Ueha S, Inadera H, Matsushima K. 2004. Endocrine disruptors (environmental estrogens) enhance autoantibody production by B1 cells. Toxicol Sci . 81:139-47.
Ito T , Ishikawa S, Sato T, Akadegawa K, Yurino H, Kitabatake M, Hontsu S, Ezaki T, Kimura H, Matsushima K. 2004. Defective B1 cell homing to the peritoneal cavity and preferential recruitment of B1 cells in the target organs in a murine model for systemic lupus erythematosus. J Immunol . 172:3628-34.
Hontsu S, Yoneyama H, Ueha S, Terashima Y, Kitabatake M, Nakano A, Ito T , Kimura H, Matsushima K. 2004. Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice. Int Immunopharmacol . 4:1785-93.