IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity
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 UMC, Amsterdam, Netherlands; 3Departm...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-01-01
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| Series: | ImmunoTargets and Therapy |
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| Online Access: | https://www.dovepress.com/iga-and-fcalphari-versatile-players-in-homeostasis-infection-and-autoi-peer-reviewed-article-ITT |
| _version_ | 1818871720306540544 |
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| author | van Gool MMJ van Egmond M |
| author_facet | van Gool MMJ van Egmond M |
| author_sort | van Gool MMJ |
| collection | DOAJ |
| description | 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 UMC, Amsterdam, Netherlands; 3Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCorrespondence: Marjolein van Egmond Tel +31204448080Email m.vanegmond@amsterdamumc.nlAbstract: 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 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 |
| first_indexed | 2024-12-19T12:27:24Z |
| format | Article |
| id | doaj.art-2bb121f618f946efb8f3f41303d18622 |
| institution | Directory Open Access Journal |
| issn | 2253-1556 |
| language | English |
| last_indexed | 2024-12-19T12:27:24Z |
| publishDate | 2021-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | ImmunoTargets and Therapy |
| spelling | doaj.art-2bb121f618f946efb8f3f41303d186222022-12-21T20:21:31ZengDove Medical PressImmunoTargets and Therapy2253-15562021-01-01Volume 935137260848IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunityvan Gool MMJvan Egmond MMelissa 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 UMC, Amsterdam, Netherlands; 3Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCorrespondence: Marjolein van Egmond Tel +31204448080Email m.vanegmond@amsterdamumc.nlAbstract: 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 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, autoimmunityhttps://www.dovepress.com/iga-and-fcalphari-versatile-players-in-homeostasis-infection-and-autoi-peer-reviewed-article-ITTneutrophilcd89mucosainfectioninflammationautoimmunity |
| spellingShingle | van Gool MMJ van Egmond M IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity ImmunoTargets and Therapy neutrophil cd89 mucosa infection inflammation autoimmunity |
| title | IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity |
| title_full | IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity |
| title_fullStr | IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity |
| title_full_unstemmed | IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity |
| title_short | IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity |
| title_sort | iga and fc alpha ri versatile players in homeostasis infection and autoimmunity |
| topic | neutrophil cd89 mucosa infection inflammation autoimmunity |
| url | https://www.dovepress.com/iga-and-fcalphari-versatile-players-in-homeostasis-infection-and-autoi-peer-reviewed-article-ITT |
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