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-α–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-γ 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_H1/T_H2 cytokine balance toward IL-4, resulting in sustainable IDO suppression.

Key words: Der p 1, IDO, dendritic cells, T_H2 cells, asthma

Abbreviations used: DC, Dendritic cell, HDM, House dust mite, iDC, Immature dendritic cell, IDO, Indoleamine 2, 3-dioxygenase, mDC, Mature dendritic cell, 1-MT, 1-Methyl DL-tryptophan, TNFR, TNF-α receptor, UK, United Kingdom