Der p 1 suppresses indoleamine 2, 3-dioxygenase in dendritic cells from house dust mite-sensitive patients with asthma.
BACKGROUND
Indoleamine 2, 3-dioxygenase (IDO), a tryptophan-degrading enzyme in dendritic cells (DCs), mediates an immunosuppressive effect on activated T lymphocytes. However, little is known about the effect of Der p 1 on IDO in human DCs.


OBJECTIVE
The aim was to investigate the effect of Der p 1 on the expression and activity of IDO in monocyte-derived DCs from house dust mite (HDM)-sensitive patients with asthma.


METHODS
Using real-time RT-PCR and HPLC, the expression and activity of IDO were assessed in TNF-alpha-induced mature DCs from HDM-sensitive and nonatopic patients with asthma in response to Der p 1 exposure ex vivo. We also monitored the alteration of IDO activity in Der p 1-pulsed DCs after the coincubation with autologous T cells.


RESULTS
With a reliance on its protease activity, Der p 1 suppressed functional IDO in DCs from HDM-sensitive patients with asthma but enhanced IDO activity in DCs from nonatopic patients with asthma. This suppression was maintained by the reciprocally induced IL-4 from the coculturing autologous HDM-sensitive T cells. Conversely, the upregulation of IDO activity in Der p 1-pulsed DCs was maintained by IFN-gamma released from autologous nonatopic T cells and the regulatory T-cell subset. Der p 1 pulsation to sensitive DCs failed to raise regulatory T cells but raised progenitor fractions from cloned HDM-sensitive CD4(+) cells through direct contact and soluble mediators.


CONCLUSIONS
House dust mite-sensitive DCs exposed to Der p 1 downregulated IDO activity and tipped the T(H)1/T(H)2 cytokine balance toward IL-4, resulting in sustainable IDO suppression.
Maneechotesuwan
Kittipong
K
Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. sikmn@mahidol.ac.th
Wamanuttajinda
Valla
V
Kasetsinsombat
Kanda
K
Huabprasert
Sukit
S
Yaikwawong
Metha
M
Barnes
Peter J
PJ
Wongkajornsilp
Adisak
A
D039741:Antigens, Dermatophagoides / Q000276:immunology* / Q000494:pharmacology; D060829:Arthropod Proteins; D001249:Asthma / Q000201:enzymology / Q000276:immunology*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C508598:IL4 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1