The Role of IgG4 in the Fine Tuning of Tolerance in IgE-Mediated Allergy and Cancer
1
The Interuniversity Messerli Research Institute of the University of Veterinary Medicine, Medical University of Vienna and University of Vienna, Veterinaerplatz 1, 1210 Vienna, Austria
2
Institute Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Division of Comparative Immunology and Oncology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
3
St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, 9th Floor, Tower Wing, Guy’s Hospital, London SE1 9RT, UK
4
Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, King’s College London, Guy’s Cancer Centre, London SE1 9RT, UK
5
Department of Physical Medicine, Rehabilitation and Occupational Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(14), 5017; https://doi.org/10.3390/ijms21145017
Received: 23 June 2020
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Revised: 9 July 2020
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Accepted: 10 July 2020
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Published: 16 July 2020
(This article belongs to the Special Issue Immunoglobulins in Inflammation)
Among the four immunoglobulin G (IgG) subclasses, IgG4 is the least represented in serum of a healthy human and it is considered an “odd” antibody. The IgG4 antibody has unique structural features that affect its biological function. These include the ability to undergo antigen-binding fragment (Fab)-arm exchange, to create fragment crystallizable (Fc) – Fc binding with other IgG4 and other IgG subclass antibodies, have a unique affinity profile for Fc gamma receptors (FcγRs) and no binding to complement component C1q. Altogether, these characteristics support anti-inflammatory roles of IgG4 leading to immune tolerance. Under conditions of chronic antigenic stimulation and Th2-type inflammation, both tissue and serum IgG4 levels are increased. This review seeks to highlight how in allergen immunotherapy IgG4 can confer a protective role as a “blocking” antibody and safeguard from subsequent allergen exposure, while IgG4 can confer immunomodulatory functions to support malignancy. While Th2 conditions drive polarization of macrophages to the M2a subtype, chronic antigen stimulation drives B cell class switching to IgG4 to further support phenotypical macrophage changes towards an M2b-like state. M2b-like macrophages can secrete chemokine (C-C motif) ligand 1 (CCL1) and interleukin-10 (IL-10) to support regulatory cell recruitment and to further shape a tolerogenic microenvironment. Thereby, IgG4 have a Janus-faced role, favorable in allergy but detrimental in cancer.
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Keywords:
allergy; cancer; IgG4; immunotolerance; M2b-like macrophages; CCL1-CCR8 Tregs; regulatory cells
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MDPI and ACS Style
Bianchini, R.; Karagiannis, S.N.; Jordakieva, G.; Jensen-Jarolim, E. The Role of IgG4 in the Fine Tuning of Tolerance in IgE-Mediated Allergy and Cancer. Int. J. Mol. Sci. 2020, 21, 5017. https://doi.org/10.3390/ijms21145017
AMA Style
Bianchini R, Karagiannis SN, Jordakieva G, Jensen-Jarolim E. The Role of IgG4 in the Fine Tuning of Tolerance in IgE-Mediated Allergy and Cancer. International Journal of Molecular Sciences. 2020; 21(14):5017. https://doi.org/10.3390/ijms21145017
Chicago/Turabian StyleBianchini, Rodolfo, Sophia N. Karagiannis, Galateja Jordakieva, and Erika Jensen-Jarolim. 2020. "The Role of IgG4 in the Fine Tuning of Tolerance in IgE-Mediated Allergy and Cancer" International Journal of Molecular Sciences 21, no. 14: 5017. https://doi.org/10.3390/ijms21145017
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