The era of the immunoglobulin A Fc receptor FcαRI; its function and potential as target in disease.
Immunoglobulin A (IgA) is the most prevalent antibody at mucosal sites, and has an important role in defense by preventing invasion of pathogens. Traditionally, IgA has been thought of as a non-inflammatory antibody that helps to maintain homeostasis in the mucosa. However, in the last decade it has become clear that IgA is a very potent stimulus to initiate pro-inflammatory cellular processes, especially after triggering the IgA Fc receptor (FcαRI) on neutrophils. It was furthermore described that FcαRI acts as a regulator between anti- and pro-inflammatory responses of IgA. Although neutrophil activation is beneficial in (mucosal) infections, abnormal or excessive IgA immune complexes can induce disproportionate neutrophil migration and in this way initiate a perpetuating neutrophil recruitment and activation loop, which will result in severe tissue damage. Increasing evidence on this process plays a detrimental role in several diseases, including autoimmune IgA blistering diseases, a subtype of rheumatoid arthritis and ulcerative colitis. Inhibiting FcαRI-mediated activation may dampen inflammation in these patients. This process also opens up the possibility of targeting FcαRI in antibody immunotherapy of cancer. Thus, interfering with IgA-mediated FcαRI activation may represent an attractive novel therapeutic strategy for multiple maladies.
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Esil
E
Aleyd
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Marieke H
MH
Heineke
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Marjolein
M
van Egmond
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D007167:Immunotherapy; D008024:Ligands; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D009928:Organ Specificity / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011961:Receptors, Fc / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D008024:Ligands; D011961:Receptors, Fc
CD89; IgA; autoimmune diseases; cancer; inflammation; neutrophil