Proprietà immunoregolatorie del DNA circolante

Circulating DNA (cDNA) is detectable at low concentration in the plasma of healthy subjects and at high concentrations in diseases as tumors and vasculitides. DNA is considered a danger signal mediating pro-inflammatory reactions after binding to DNA sensors. However, this view conflicts with recent data on DNA-sensors function and with the presence of elevated cDNA concentrations in tumor patients, where processes related to immune tolerance generally prevail, leading to variable degree of immunodeficiency. Hence, the biologic role of cDNA is controversial. Previous data from our group suggested that DNA may exert immunoregulatory functions in vitro interacting with HLA class II molecules. Here, we show that DNA, mainly acting on APC, binds to mouse MHC class II molecules and mediates immune regulatory activities inhibiting antigen specific immune responses and inducing Treg. These activities may be dependent on hindrance of antigen binding to MHC class II molecules and intracellular cell signaling. Interestingly, exogenously administered cDNA exerted immune regulatory functions in vivo. In particular, it protected lupus-prone mice from disease progression and favored tumor growth in tumor-challenged mice. Hence, this study unveils unprecedented biologic functions of cDNA that may have pathogenic relevance in cancer.