| Akio Ohta|
Principal Research Scientist
Department: New England Inflammation & Tissue Protection Institute
Department 2: School of Pharmacy
Office: 113 Mugar Life Sciences Building
Regulation of immune/inflammatory responses
Inflammation plays important roles in a variety of human diseases. For example, allergic and autoimmune disorders are caused by uncontrolled inflammatory responses against exogenous and endogenous antigens, respectively. The lack of efficient immune responses against abnormal cells may lead to tumor progression. When infected to virus, strong anti-viral responses will be able to control the virus, but this may lead to severe tissue inflammation and serious tissue dysfunction as a result of massive elimination of virus-infected cells. On the other hand, insufficient anti-viral immune responses will allow persistent infection and repeated induction of inflammation and tissue remodeling (chronic inflammation) may result in fibrosis. Sepsis is life-threatening in two different ways: bacterial products induce strong systemic inflammatory responses which often causes septic shock, and following immune unresponsiveness loses control against infection.
The understanding of regulatory mechanisms of immune and inflammatory responses is important to develop a new therapeutic option for treatment of inflammatory disorders. Based on our finding of adenosine A2A receptor as an important anti-inflammatory mechanism, we are examining the role of this pathway during course of inflammation using animal models of above mentioned disorders. The intervention to inflammation is being examined by activating or inhibiting adenosine-A2A receptor pathway. Our research also includes challenges to find more immunomodulating mechanisms and to develop new experimental models of diseases for which current lack of appropriate animal model is inhibiting the advance of research
1. Ohta A, Sitkovsky M. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 2001;414:916-20.
2. Sitkovsky MV, Lukashev D, Apasov S, Kojima H, Koshiba M, Caldwell C, Ohta A, Thiel M. Physiological control of immune response and inflammatory tissue damage by hypoxia inducible factors and adenosine A2A receptors. Annu Rev Immunol 2004;22:657-82
3. Lukashev D, Ohta A, Apasov S, Chen JF, Sitkovsky M. Physiologic attenuation of proinflammatory transcription by the Gs protein-coupled A2A adenosine receptor in vivo. J Immunol 2004;173:21-4.
4. Thiel M, Chouker A, Ohta A, Jackson E, Caldwell C, Smith P, Lukashev D, Bittmann I, Sitkovsky MV. Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury. PLoS Biol 2005;3:e174.
5. Sitkovsky MV, Ohta A. The "danger" sensors that STOP immune response: The A2 adenosine receptors? Trends Immunol 2005;26:299-304.
6. Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D, Wong MK, Huang X, Caldwell S, Liu K, Smith P, Chen JF, Jackson EK, Apasov S, Abrams S, Sitkovsky M. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U.S.A. 2006;103:13132-7.
7. Ohta A, Lukashev D, Jackson EK, Fredholm BB, Sitkovsky M. 1,3,7-Trimethylxanthine (caffeine) may exacerbate acute inflammatory liver injury by weakening the physiological immunosuppressive mechanism. J Immunol 2007;179:7431-8
8. Ohta A, Kjaergaard J, Sharma S, Mohsin M, Goel N, Madasu M, Fradkov E, Ohta A, Sitkovsky M. In vitro negative selection of T cells that are resistant to A2 adenosine receptor-mediated immunosuppression. Br J Pharmacol 2009;156:297-306.