Potential regulatory functions of indoleamine 2,3-dioxygenase expression by FcERI⁺ monocytes from atopic individuals

Background: New immunomodulatory signals have been detected after the engagement of the high affinity receptor for IgE, FcERI, on atopic monocytes. The processes that lead to the establishment of allergic inflammation are better known than those that limit, turn off or prevent allergy. This study describes the involvement of the tryptophan degradation pathway after FcERI ligation that might regulate T cell responses in atopic disorders. Methods/Data base: A differential cDNA bank of FcERI-stimulated and unstimulated monocytes from an atopic donor was established. By means of suppression subtractive hybridization, genes coding for kynurenine 3-monooxygenase and subsequently indoleamine 2,3-dioxygenase have been identified to be overexpressed in FcERI-activated monocytes. These genes code for two enzymes involved in the degradation of the essential amino acid tryptophan. Results: Functionally, suppression of T cell proliferation by the degradation of tryptophan from the medium could be demonstrated upon induction of indoleamine 2,3-dioxygenase after ligation of FcERI. Conclusion: FcERI⁺ antigen-presenting cells may regulate T cell responses in atopic disorders by interfering with the local tryptophan level. It is tempting to speculate that indoleamine 2,3-dioxygenase expression in antigen-presenting cells of symptomatic and asymptomatic atopic individuals is regulated differently.