U.S. Department of Defense


Date of this Version



Published in Clinical Immunology (2011) 141, 205–217; doi:10.1016/j.clim.2011.08.004


Mounting evidence suggests that helminth infections protect against autoimmune diseases. As helminths cause chronic IgE-mediated activation of basophils and mast cells we hypothesized that continuous activation of these cells could prevent diabetes onset in nonobese diabetic (NOD) mice in the absence of infection. Anti-FcεR1 activated basophils and mast cells and resulted in the release of IL-4 and histamine into the bloodstream. Anti-FcεR1-treated NOD mice showed a type 2 shift in insulin-specific antibody production and exhibited significant delays in diabetes onset. IL-4 responses played a partial role as the protective effect of anti-FcεR1 therapy was diminished in IL-4-deficient NOD mice. In contrast, histamine signaling was not required as anti-FcεR1-mediated protection was not reduced in mice treated with histamine receptor blockers. These results demonstrate that anti-FcεR1 therapy delays diabetes onset in NOD mice and suggest that chronic basophil and mast cell activation may represent a new avenue of therapy for Th1-associated autoimmune diseases.