Anti-FcεR1 antibody injections activate basophils and mast cells and delay Type 1 diabetes onset in NOD mice

Authors

Marc P. Hübner, University Hospital BonnFollow
David Larson, Uniformed Services University of the Health SciencesFollow
Marina N. Torrero, Uniformed Services University of the Health SciencesFollow
Ellen Mueller, Uniformed Services University of the Health SciencesFollow
Yinghui Shi, Uniformed Services University of the Health SciencesFollow
Kristin E. Killoran, Uniformed Services University of the Health SciencesFollow
Edward Mitre, Uniformed Services University of the Health SciencesFollow

Date of this Version

2011

Comments

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

Abstract

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.