Steroids inhibit uptake and/or processing but not presentation of antigen by airway dendritic cells.
Recent studies from our laboratory indicate that local and (particularly) systemic steroids can modulate the traffic of dendritic cells (DC) through resting and inflamed airway epithelial tissues. The present report focuses upon the T-cell activating properties of DC, which are controlled by granulocyte-macrophage colony-stimulating factor (GM-CSF) signals, and in particular the question of whether the DC-stimulating effects of GM-CSF are susceptible to regulation by steroids. We present evidence that while dexamethasone inhibited GM-CSF-dependent uptake and/or processing of exogenous antigen by DC, it was ineffective in blocking the presentation of preprocessed self antigen to alloreactive T cells in a one-way mixed lymphocyte reaction (MLR). Associated GM-CSF-induced up-regulation of major histocompatability complex (MHC) class II and CTLA4 ligand expression by DC were also unaffected by dexamethasone phosphate (DX), reinforcing the view that the inhibitory effects of steroids on the T-cell activating functions of DC are restricted to steps upstream from presentation of processed antigen to the T-cell receptor (TCR). These findings have potentially important implications in relation to the use of topical steroids in the treatment of atopic asthma, a disease in which local T-cell activation in airway tissue is a key pathogenic factor, and which furthermore is characterized by intense production of GM-CSF within the airway epithelium.
Holt
P G
PG
Institute for Child Health Research, West Perth, Australia.
Thomas
J A
JA
D000069594:Abatacept; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D060908:CTLA-4 Antigen; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D018796:Immunoconjugates; D007959:Lymphocyte Culture Test, Mixed; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D012137:Respiratory System / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; D005938:Glucocorticoids; D000949:Histocompatibility Antigens Class II; D018796:Immunoconjugates; D011994:Recombinant Proteins; D000069594:Abatacept; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin