Counter regulation of the high affinity IgE receptor, FcεRI, on human airway dendritic cells by IL-4 and IL-10

Background: Immunoglobulin E is a signalling molecule within the environment of the respiratory tract, the high affinity receptor for which, Fc epsilon RI, is expressed by dendritic cells (DC). Little is known, however, of the expression and function of Fc epsilon RI on DC in the human respiratory tract. Methods: CD1c+ DC were purified from surgically resected nasal turbinates of 11 atopic and 12 nonatopic patients with chronic rhinosinusitis. Expression of Fc epsilon RI was determined by flow cytometry. Cytokine production by DC was determined by cytometric bead array. Results: Expression of Fc epsilon RI was significantly elevated on respiratory tract dendritic cells (RTDC) from atopic as compared to nonatopic patients. Activation of RTDC through Fc epsilon RI induced production of the pro-inflammatory cytokines IL-6 and TNF-alpha, and the anti-inflammatory cytokine IL-10. The production of IL-6 and TNF-alpha was elevated in atopic compared to nonatopic patients studied. Conversely IL-10 production was elevated in nonatopic patients. Concomitant activation of Fc epsilon RI and stimulation of RTDC with IL-4 inhibited production of IL-10 by RTDC. Neutralization experiments with anti-IL-10 Ab enhanced whereas addition of exogenous IL-10 to RTDC inhibited Fc epsilon RI-mediated inflammatory cytokine production. Conclusion: The function of Fc epsilon RI on RTDC from patients with rhinosinusitis is susceptible to counter regulation by IL-4 and IL-10.