IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity

IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity

Blog Article

Melissa Maria Johanna van Gool,1,2 Marjolein van Egmond1– 3 1Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; 2Amsterdam institute for Infection and Immunity, Amsterdam Kids Balboa HOODIES UMC, Amsterdam, Netherlands; 3Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCorrespondence: Marjolein van Egmond Tel +31204448080Email [email protected]: Mucosal surfaces constitute the frontiers of the body and are the biggest barriers of our body for the outside world.Immunoglobulin A (IgA) is the most abundant antibody class present at these sites.

It passively contributes to mucosal homeostasis via immune exclusion maintaining a tight balance between tolerating commensals and providing protection against pathogens.Once pathogens have succeeded in invading the epithelial barriers, IgA has an active role in host-pathogen defense by activating myeloid cells through divers receptors, including its Fc receptor, FcαRI (CD89).To evade elimination, several pathogens secrete proteins that interfere with either IgA Hoodie neutralization or FcαRI-mediated immune responses, emphasizing the importance of IgA-FcαRI interactions in preventing infection.Depending on the IgA form, either anti- or pro-inflammatory responses can be induced.

Moreover, the presence of excessive IgA immune complexes can result in continuous FcαRI-mediated activation of myeloid cells, potentially leading to severe tissue damage.On the one hand, enhancing pathogen-specific mucosal and systemic IgA by vaccination may increase protective immunity against infectious diseases.On the other hand, interfering with the IgA-FcαRI axis by monovalent targeting or blocking FcαRI may resolve IgA-induced inflammation and tissue damage.This review describes the multifaceted role of FcαRI as immune regulator between anti- and pro-inflammatory responses of IgA, and addresses potential novel therapeutic strategies that target FcαRI in disease.

Keywords: neutrophil, CD89, mucosa, infection, inflammation, autoimmunity.