Immunotolerant indoleamine-2,3-dioxygenase increases in condyloma acuminata

Abstract

Background

The tryptophan-depleting enzyme indoleamine-2,3-dioxygenase (IDO) is critical for the regulation of immune tolerance and plays an important role in immune-associated skin diseases.

Objectives

To analyze the level of IDO in condyloma acuminata (CA) and its role in this condition.

Methods

IDO expression was assessed in the skin and peripheral blood of healthy subjects and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T cell mitogen (PHA)-stimulated T cell proliferation were explored.

Results

IDO median fluorescence intensities (MFIs) in peripheral blood mononuclear cells (PBMCs) from CA patients were similar to those from healthy controls. Immunohistochemistry showed that IDO(+) cells were rare in normal skin and the control skin of CA patients but were greatly accumulated in wart tissue. Most fluorescence signals of IDO(+) cells were not overlapping with those of CD1a(+) Langerhans cells (LCs). HPV DNA probe in situ hybridization showed a large number of IDO(+) cells in the HPV(-) site. Keratinocytes (KCs) in the skin of healthy subjects and the circumcised skin of CA patients could minimally transform tryptophan into kynurenine, but IDO-competent epidermal cells from warts could transform tryptophan. In addition, these IDO-competent epidermal cells could inhibit PHA-stimulated T cell proliferation. The addition of an IDO inhibitor 1-MT restored the inhibited T cell proliferation.

Conclusion

Abnormally localized high IDO expression might be involved in the formation of a local immune tolerant microenvironment.

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