title: GM-CSF modulates autoantibody production and skin blistering in experimental epidermolysis bullosa acquisita.
abstract: GM-CSF activates hematopoietic cells and recruits neutrophils and macrophages to sites of inflammation. Inhibition of GM-CSF attenuates disease activity in models of chronic inflammatory disease. Effects of GM-CSF blockade were linked to modulation of the effector phase, whereas effects on early pathogenic events, for example, Ab production, have not been identified. To evaluate yet uncharacterized effects of GM-CSF on early pathogenic events in chronic inflammation, we employed immunization-induced epidermolysis bullosa acquisita (EBA), an autoimmune bullous disease caused by autoantibodies to type VII collagen. Compared to wild-type mice, upon immunization, GM-CSF(-/-) mice produced lower serum autoantibody titers, which were associated with reduced neutrophil numbers in draining lymph nodes. The same effect was observed in neutrophil-depleted wild-type mice. Neutrophil depletion in GM-CSF(-/-) mice led to a stronger inhibition, indicating that GM-CSF and neutrophils have additive functions. To characterize the contribution of GM-CSF specifically in the effector phase of EBA, disease was induced by transfer of anti-type VII collagen IgG into mice. We observed an increased GM-CSF expression, and GM-CSF blockade reduced skin blistering. Additionally, GM-CSF enhanced reactive oxygen species release and neutrophil migration in vitro. In immunization-induced murine EBA, treatment with anti-GM-CSF had a beneficial effect on established disease. We demonstrate that GM-CSF modulates both autoantibody production and skin blistering in a prototypical organ-specific autoimmune disease.
authors: Department of Dermatology, University of Lübeck, 23563 Lübeck, Germany.
authors: Unni Krishna S R L
authors: UK
authors: Samavedam
authors: Hiroaki
authors: H
authors: Iwata
authors: Susen
authors: S
authors: Müller
authors: Franziska S
authors: FS
authors: Schulze
authors: Andreas
authors: A
authors: Recke
authors: Enno
authors: E
authors: Schmidt
authors: Detlef
authors: D
authors: Zillikens
authors: Ralf J
authors: RJ
authors: Ludwig
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D024143:Collagen Type VII / Q000276:immunology; D004195:Disease Models, Animal; D016107:Epidermolysis Bullosa Acquisita / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D012867:Skin / Q000276:immunology
chemical_list: D001323:Autoantibodies; D024143:Collagen Type VII; D007074:Immunoglobulin G; D017382:Reactive Oxygen Species; D016178:Granulocyte-Macrophage Colony-Stimulating Factor