IgG Signalling Involves in Skin Inflammation of Atopic Dermatitis

Abstract

Atopic dermatitis (AD) patients usually have elevated serum IgE that is thought inducing inflammation upon binding to allergen. However, the role of IgE-producing B cells and other isotypes of immunoglobulin, such as IgG, in AD are not clear and rarely explored. This study aimed to investigate the role of IgE-producing B cells and other isotypes of immunoglobulin, particularly IgG, in skin lesion of AD. BCR repertoires were analysed using mRNA prepared from skin lesions and peripheral blood mononuclear cells (PBMCs) from AD patients and non-allergic healthy subjects. Single-cell RNA sequencing data of AD lesions from published literature were extracted to analyse the function of IgG. BCR repertoires from skin lesion and PBMCs clustered distinctly, and PBMCs showed higher interindividual similarity compared to those from the skin. The proportions of IGHM, IGHD, IGHA, IGHG and IGHE varied among skin lesion and PBMCs of AD patients and healthy individuals, and IGHG was significantly increased in AD lesion. IGHG showed biased VH usage, with dominance of V1-58, V1-8, V3-13 and V3-73. The much higher hyperexpanded clonality and lower diversity of IGHG repertoire in skin than those of the PBMCs, suggested the clonal expansion of IgG⁺ B cells in the skin. Pathways related with IgG activation were enriched in AD skin, and macrophages may be activated by IgG and promote skin inflammation. In conclusion, skin is not the main production site for IgE in AD. IgG may involve in promoting Th2 inflammation in AD skin through macrophages.