Abstract
Despite the well-recognized involvement of immunoglobulin (Ig) A in mucosal immunity, the function of its receptor, FcαRI (CD89), is poorly understood. The ability of FcαRI to activate leukocytes seems to conflict with the proposed anti-inflammatory activity of secretory IgA. We show here that in a transgenic mouse model, inflammatory mediators induced expression of FcαRI on Kupffer cells, which enabled efficient phagocytosis in vivo of bacteria coated with serum IgA. Secretory IgA did not initiate phagocytosis. Therefore, interactions between serum IgA and FcαRI on Kupffer cells may provide a ‘second line of defense’ in mucosal immunity, by eliminating invasive bacteria entering through the portal circulation and thus preventing disease.
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Acknowledgements
The authors thank T. Hesp for animal care, J. Duijs (Leiden University Medical Center) for technical assistance with high-performance liquid chromatography experiments, and M. Schipper (Department of Pathology, University Medical Center Utrecht) for advice on human liver biopsies. We thank L. Shen (Dartmouth Medical School, New Hampshire) and G. Vidarsson for reviewing the manuscript. TNF-α was a gift from W. Buurman (Maastricht University, The Netherlands). This work was supported by Netherlands Organization for Scientific Research grant 901-12-214.
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van Egmond, M., van Garderen, E., van Spriel, A. et al. FcαRI-positive liver Kupffer cells: Reappraisal of the function of immunoglobulin A in immunity. Nat Med 6, 680–685 (2000). https://doi.org/10.1038/76261
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DOI: https://doi.org/10.1038/76261
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