Toll-like receptor triggering augments activation of human mast cells by anti-citrullinated protein antibodies

Abstract

Our data show that synovial mast cells express FcγRIIA and that mast cells can be activated by IgG-ACPA and TLR ligands. Importantly, combined stimulation via TLRs and immune complexes leads to synergy in cytokine production. These findings suggest mast cells are important targets for TLR ligands and immune complexes, and that combined activation of mast cells via these pathways greatly enhances inflammation in synovial tissue of RA patients.

Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity

“…This process causes a vicious cycle wherein each disease flare can initiate further autoantibody production and tissue injury (107)(108)(109). Furthermore, combined TLR-and Fc receptor-mediated activation of myeloid cells often leads to an enhanced inflammatory response that is thought to contribute to the chronicity of inflammation (51,94,110,111). Therefore, those self-antigens that can most potently activate B cells because they are TLR ligands may also potently enhance pathogenic inflammatory responses (Figure 3).…”

“…Activating Fc receptors are expressed by a variety of cells, particularly by immune cells of the myeloid lineage. Autoantibodies have been shown to activate these immune cells through FcγR-dependent pathways (92)(93)(94). In vivo, FcγR-deficient mice often show decreased autoimmunity (95,96).…”

Association between rheumatoid arthritis and systemic mastocytosis: a case report and literature review

“…Indeed, once activated (by ACPA for instance), MCs produce large amount of IL-8, a potent activator of neutrophil chemotaxis [31]. MCs can also produce IL-1, TNF and IL-17, all responsible for synovial fibroblast activation and deleterious consequences on cartilage.…”

“…In addition to toll-like crosslinking FcRIIA [31]. Mast cells can also interact directly with T cell, contributing to T cell subset expansion [32] or activation [33] but also changing their own phenotype [34].…”

Are Basophils and Mast Cells Masters in HIV Infection?

“…Although the physiological role of mast cells and basophils remains enigmatic, there is now increasing evidence that these cells are critically involved not only in allergic disorders but also in autoimmune and infectious diseases, immunodeficiencies, and cancer [13,14,15,17,83], with multifaceted roles due to their ability to mediate both pro- and anti-inflammatory/immunomodulatory responses [21,23,84]. …”