title: Anti-FcεR1 antibody injections activate basophils and mast cells and delay Type 1 diabetes onset in NOD mice.
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.
authors.affiliation: Dept. of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Huebner@microbiology-bonn.de
authors.forename: Marc P
authors.initials: MP
authors.lastname: Hübner
authors.forename: David
authors.initials: D
authors.lastname: Larson
authors.forename: Marina N
authors.initials: MN
authors.lastname: Torrero
authors.forename: Ellen
authors.initials: E
authors.lastname: Mueller
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Shi
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Killoran
authors.forename: Edward
authors.initials: E
authors.lastname: Mitre
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006373:Helminthiasis / Q000276:immunology; D006633:Histamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007328:Insulin / Q000276:immunology; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D018448:Models, Immunological; D017455:Receptors, IgE / Q000037:antagonists & inhibitors* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D006633:Histamine Antagonists; D007328:Insulin; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E