Counter regulation of the high affinity IgE receptor, FcepsilonRI, 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, FcepsilonRI, is expressed by dendritic cells (DC). Little is known, however, of the expression and function of FcepsilonRI 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 FcepsilonRI was determined by flow cytometry. Cytokine production by DC was determined by cytometric bead array.


RESULTS
Expression of FcepsilonRI was significantly elevated on respiratory tract dendritic cells (RTDC) from atopic as compared to nonatopic patients. Activation of RTDC through FcepsilonRI 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 FcepsilonRI 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 FcepsilonRI-mediated inflammatory cytokine production.


CONCLUSIONS
The function of FcepsilonRI on RTDC from patients with rhinosinusitis is susceptible to counter regulation by IL-4 and IL-10.
Faith
A
A
MRC-Asthma UK Centre in Allergic Mechanisms of Asthma, King's College, London, UK.
Singh
N
N
Chevretton
E
E
Roberts
D
D
Lee
T
T
Corrigan
C
C
Hawrylowicz
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017455:Receptors, IgE / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D055815:Young Adult
D017455:Receptors, IgE; D016753:Interleukin-10; D015847:Interleukin-4