IgG-aggregates rapidly up-regulate FcgRI expression at the surface of human neutrophils in a FcgRII-dependent fashion: A crucial role for FcgRI in cellular responsiveness.

Huot, S.; Laflamme, C.; Fortin, P. R.; Boilard, E.; Pouliot, M.

doi:10.1101/2020.03.04.975094

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bioRxiv · 10.1101/2020.03.04.975094

IgG-aggregates rapidly up-regulate FcgRI expression at the surface of human neutrophils in a FcgRII-dependent fashion: A crucial role for FcgRI in cellular responsiveness.

Huot, S.·Laflamme, C.·Fortin, P. R.·Boilard, E.·Pouliot, M.

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Abstract

Autoimmune complexes are an important feature of several autoimmune diseases such as lupus, as they contribute to tissue damage through the activation of immune cells. Neutrophils, key players in lupus, interact with immune complexes through Fc gamma receptors (FcgR). Incubation of neutrophils with aggregated-IgGs caused degranulation and increased the surface expression of FcgRI within minutes in a concentration-dependent fashion. After 30 min, IgG aggregates (1 mg/ml) up-regulated FcgRI by 4.95 {+/-} 0.45-fold. FcgRI-positive neutrophils reached 67.24% {+/-} 6.88% on HA-IgGs stimulated neutrophils, from 3.12% {+/-} 1.62% in non-stimulated cells, ranking IgG-aggregates among the most potent known agonists. FcgRIIa, and possibly FcgRIIIa, appeared to mediate this up-regulation. Also, FcgRI-dependent signaling proved necessary for reactive oxygen species (ROS) production in response to IgG-aggregates. Finally, combinations of bacterial materials with aggregates dramatically boosted ROS production. This work suggests FcgRI as an essential component in the response of human neutrophils to immune complexes leading to the production of ROS, which may help explain how neutrophils contribute to tissue damage associated with immune complex-associated diseases, such as lupus.

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Huot, S., Laflamme, C., Fortin, P. R., Boilard, E., Pouliot, M.. 2020-03-05. IgG-aggregates rapidly up-regulate FcgRI expression at the surface of human neutrophils in a FcgRII-dependent fashion: A crucial role for FcgRI in cellular responsiveness.. https://doi.org/10.1101/2020.03.04.975094

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