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The inflammatory function of human IgA

Author:
Hansen, Ivo S., Baeten, Dominique L. P., den Dunnen, Jeroen
Source:
Cellular and molecular life sciences 2019 v.76 no.6 pp. 1041-1055
ISSN:
1420-682X
Subject:
Kupffer cells, antigen-antibody complex, celiac disease, cytokines, dendritic cells, humans, immunity, immunoglobulin A, inflammation, inflammatory bowel disease, monocytes, neoplasms, neutralization, pathogenesis, pathogens, receptors, rheumatoid arthritis, therapeutics
Abstract:
The prevailing concept regarding the immunological function of immunoglobulin A (IgA) is that it binds to and neutralizes pathogens to prevent infection at mucosal sites of the body. However, recently, it has become clear that in humans IgA is also able to actively contribute to the initiation of inflammation, both at mucosal and non-mucosal sites. This additional function of IgA is initiated by the formation of immune complexes, which trigger Fc alpha Receptor I (FcαRI) to synergize with various other receptors to amplify inflammatory responses. Recent findings have demonstrated that co-stimulation of FcαRI strongly affects pro-inflammatory cytokine production by various myeloid cells, including different dendritic cell subsets, macrophages, monocytes, and Kupffer cells. FcαRI-induced inflammation plays a crucial role in orchestrating human host defense against pathogens, as well as the generation of tissue-specific immunity. In addition, FcαRI-induced inflammation is suggested to be involved in the pathogenesis of various chronic inflammatory disorders, including inflammatory bowel disease, celiac disease, and rheumatoid arthritis. Combined, IgA-induced inflammation may be used to either promote inflammatory responses, e.g. in the context of cancer therapy, but may also provide new therapeutic targets to counteract chronic inflammation in the context of various chronic inflammatory disorders.
Agid:
6326302