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Effect of laminin-332 pemphigoid IgG on the keratinocyte transcriptome

ABSTRACT: To determine the role of laminin-332 autoantibodies in inducing a pro-inflammatory and proteolytic response by keratinocytes

ORGANISM(S): Homo sapiens

PROVIDER: GSE182644 | GEO | 2021/08/26

REPOSITORIES: GEO

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Effect of laminin-332 pemphigoid IgG on the keratinocyte transcriptome

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Project description:Intravenous immunoglobulin (IVIg) is used to treat mucous membrane pemphigoid (MMP), although its therapeutic effectivity is not sufficiently supported by randomized controlled clinical trials and its mode of action is only insufficiently understood. We have examined the effect of IVIg in a mouse model of anti-laminin 332 MMP and found that IVIg ameliorates both cutaneous and mucosal inflammatory lesions. Our investigation into the modes of action of IVIg in MMP indicated effective antiinflammatory mechanisms beyond the enhanced degradation of IgG mediated through inhibition of the neonatal Fc receptor. Our results suggest that IVIg curbs the activation of neutrophils at several levels. This includes a direct, immediate inhibitory effect on neutrophil activation by immune complexes but not C5a which blunts the release of reactive oxygen species and leukotriene B4 from neutrophils. IVIg also suppresses the formation of neutrophil extracellular traps in response to Ca2+ ionophore. In vivo treatment with IVIg altered the transcriptome of blood leukocytes and bone marrow neutrophils towards less proinflammatory phenotypes. Collectively, our results support the effectivity of IVIg in the treatment of MMP and indicate that effects on neutrophils at multiple levels may significantly contribute to its therapeutic effects.

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Intravenous immunoglobulin (IVIg) ameliorates disease in a murine model of anti-laminin 332 mucous membrane pemphigoid

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