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  • Title: Der p 1 suppresses indoleamine 2, 3-dioxygenase in dendritic cells from house dust mite-sensitive patients with asthma.
    Author: Maneechotesuwan K, Wamanuttajinda V, Kasetsinsombat K, Huabprasert S, Yaikwawong M, Barnes PJ, Wongkajornsilp A.
    Journal: J Allergy Clin Immunol; 2009 Jan; 123(1):239-48. PubMed ID: 19058839.
    Abstract:
    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. CONCLUSION: 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.
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