T regulatory cells: hypoxia-adenosinergic suppression and re-direction of the immune response.
T regulatory cells (Treg cells) suppress immune responses to maintain self tolerance, but they also protect cancerous tissues. I propose a model to potentially unify the diverse functions of Treg cells. This assumes that Treg cells provide a complementary immunological arm to a physiological tissue-protecting mechanism, driven by low oxygen tension (i.e. hypoxia) in inflamed or cancerous tissues. The cAMP-elevating A2A and A2B adenosine receptors, hypoxia inducible transcription factor 1alpha (HIF), the cAMP response element (CRE)- and hypoxia response element (HRE)-mediated transcription in Treg and effector cells have key roles in this model. Both the T cell receptor (TCR)-triggered- and HRE- and CRE-driven activities of Treg cells are required to achieve a maximal level of immune suppression.
Sitkovsky
Michail V
MV
New England Inflammation and Tissue Protection Institute, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA. m.sitkovsky@neu.edu
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia / Q000276:immunology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000276:immunology / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000276:immunology / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D000241:Adenosine