Loss of Indoleamine-2,3-Dioxygenase-1 (IDO1) in Knockout Mice Does Not Affect the Development of Skin Lesions in the Imiquimod-Induced Mouse Model of Psoriasis

Vivek Choudhary, Etsubdenk Ajebo, Rawipan Uaratanawong, Shinjini C. Spaulding, Sarah Hossack, Xunsheng Chen, Jianrui Xu, Mrunal Choudhary, Debra L. Irsik, Carlos M. Isales, Wendy B. Bollag

Research output: Contribution to journalArticlepeer-review

Abstract

Indoleamine-2,3-dioxygenase (IDO) degrades the essential amino acid tryptophan resulting in tryptophan depletion and the accumulation of catabolites such as kynurenine. The expression/activity of IDO in various cells, including macrophages and dendritic cells, results in an inhibition of T-cell responses in a number of situations, such as toward allogeneic fetuses and tissue grafts. Psoriasis is an immune-mediated skin disease involving T cells; kynureninase and its generation of catabolites downstream of IDO are reported to play an important role in this disease. We hypothesized that mice lacking the IDO1 gene would exhibit a hyperactive immune response and an exacerbation of skin lesions in the imiquimod-induced mouse model of psoriasis. Littermate wild-type and IDO1-knockout mice were treated with imiquimod for 5 days, and the severity of psoriasiform skin lesions assessed using the psoriasis area and severity index (PASI), ear edema measured using a digital caliper, and thickness of the epidermis determined by histology. Expression of pro-inflammatory mediators and tryptophan-metabolizing enzymes was monitored using quantitative RT-PCR. Imiquimod increased ear edema, PASI scores, and epidermal thickness in both WT and IDO1 knockout mice; however, there were no differences observed between the 2 genotypes. There were also no differences in imiquimod’s induction of skin inflammatory mediators, indicating no effect of IDO1 gene loss in this psoriasis model. Although these data suggest a lack of involvement of IDO1 in psoriatic skin inflammation, other possible mechanisms, such as compensatory changes in other pathways and the involvement of the IDO2 isoform, must also be considered.

Original languageEnglish (US)
JournalInternational Journal of Tryptophan Research
Volume15
DOIs
StatePublished - Feb 2022

Keywords

  • Imiquimod (IMQ)
  • T cells
  • indoleamine-2,3-dioxygenase (IDO)
  • inflammation
  • kynureninase
  • kynurenine
  • psoriasis
  • skin
  • tryptophan

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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