Gene expression of enzymes for tryptophan degradation pathway is upregulated in the skin lesions of patients with atopic dermatitis or psoriasis

Ito, Mikito; Ogawa, Katsuhiro; Takeuchi, Kaori; Nakada, Akiko; Heishi, Masayuki; Suto, Hajime; Mitsuishi, Kouichi; Sugita, Yuji; Ogawa, Hideoki; Ra, Chisei

doi:10.1016/j.jdermsci.2004.08.012

Cited by 42 publications

(35 citation statements)

References 25 publications

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“…The lack of complete reversal with this maneuver is likely to be explained by the continued accumulation of tryptophan metabolites kynurenine, 3-hydroxykyrnurenine and 3-hydroxyanthranillic acid, which suppress T cell proliferation, although we did not formally test this (59). Supporting the relevance of this mechanism in vivo, up-regulated expression of IFN-␥, IDO, and increased tryptophan degradation have been found in psoriatic skin lesions (60) and in the intrinsic resistance of Fb to Toxoplasma gondii infection (61). We did not find any evidence for the role of PG in T cell-suppressive effects by dermal Fb or BM MSC.…”

Section: Discussionmentioning

confidence: 91%

Adult Human Fibroblasts Are Potent Immunoregulatory Cells and Functionally Equivalent to Mesenchymal Stem Cells

Haniffa

Wang²,

Holtick³

et al. 2007

The Journal of Immunology

316

247

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Bone marrow mesenchymal stem cells (MSC) have potent immunosuppressive properties and have been advocated for therapeutic use in humans. The nature of their suppressive capacity is poorly understood but is said to be a primitive stem cell function. Demonstration that adult stromal cells such as fibroblasts (Fb) can modulate T cells would have important implications for immunoregulation and cellular therapy. In this report, we show that dermal Fb inhibit allogeneic T cell activation by autologously derived cutaneous APCs and other stimulators. Fb mediate suppression through soluble factors, but this is critically dependent on IFN-γ from activated T cells. IFN-γ induces IDO in Fb, and accelerated tryptophan metabolism is at least partly responsible for suppression of T cell proliferation. T cell suppression is reversible, and transient exposure to Fb during activation reprograms T cells, increasing IL-4 and IL-10 secretion upon restimulation. Increased Th2 polarization by stromal cells is associated with amelioration of pathological changes in a human model of graft-vs-host disease. Dermal Fb are highly clonogenic in vitro, suggesting that Fb-mediated immunosuppression is not due to outgrowth of rare MSC, although dermal Fb remain difficult to distinguish from MSC by phenotype or transdifferentiation capacity. These results suggest that immunosuppression is a general property of stromal cells and that dermal Fb may provide an alternative and accessible source of cellular therapy.

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Section: Discussionmentioning

confidence: 91%

Adult Human Fibroblasts Are Potent Immunoregulatory Cells and Functionally Equivalent to Mesenchymal Stem Cells

Haniffa

Wang²,

Holtick³

et al. 2007

The Journal of Immunology

316

247

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show abstract

“…Of the two models, the NC model has been more widely used to compare the phenotype between human AD patients and the mice, to explore causative genes (Ito et al, 2004, Ogawa et al, 2005, Fallon et al, 2009, Jung et al, 2011 and genetic loci (Kohara et al, 2001), and for drug development (Yamamoto et al, 2007, Shah et al, 2010 and the therapy of human AD (Takeda and Gelfand, 2009). Therefore, the immunological, pathological and genetic characteristics have been extensively examined in detail.…”

Section: Details Of the Nc Modelmentioning

confidence: 99%

Mouse Models for Atopic Dermatitis Developed in Japan

Yonekawa¹,

Takada²,

Shitara³

et al. 2012

Atopic Dermatitis - Disease Etiology and Clinical Management

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“…In mammals, tryptophan catabolism is well-known, but the amino acid and its degradation products are still under investigation because they are implicated in several nervous system pathologies (Fujigaki et al 1998;Wonodi and Schwarcz 2010;Campesan et al 2011) and in psoriasis (Ito et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Tryptophan catabolism via kynurenine production in Streptomyces coelicolor: identification of three genes coding for the enzymes of tryptophan to anthranilate pathway

Zummo

Marineo

Pace

et al. 2012

Appl Microbiol Biotechnol

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Most enzymes involved in tryptophan catabolism via kynurenine formation are highly conserved in Prokaryotes and Eukaryotes. In humans, alterations of this pathway have been related to different pathologies mainly involving the central nervous system. In Bacteria, tryptophan and some of its derivates are important antibiotic precursors. Tryptophan degradation via kynurenine formation involves two different pathways: the eukaryotic kynurenine pathway, also recently found in some bacteria, and the tryptophan-to-anthranilate pathway, which is widespread in microorganisms. The latter produces anthranilate using three enzymes also involved in the kynurenine pathway: tryptophan 2,3-dioxygenase (TDO), kynureninase (KYN), and kynurenine formamidase (KFA). In Streptomyces coelicolor, where it had not been demonstrated which genes code for these enzymes, tryptophan seems to be important for the calcium- dependent antibiotic (CDA) production. In this study, we describe three adjacent genes of S. coelicolor (SCO3644, SCO3645, and SCO3646), demonstrating their involvement in the tryptophan-to-anthranilate pathway: SCO3644 codes for a KFA, SCO3645 for a KYN and SCO3646 for a TDO. Therefore, these genes can be considered as homologous respectively to kynB, kynU, and kynA of other microorganisms and belong to a constitutive catabolic pathway in S. coelicolor, which expression increases during the stationary phase of a culture grown in the presence of tryptophan. Moreover, the S. coelicolor ΔkynU strain, in which SCO3645 gene is deleted, produces higher amounts of CDA compared to the wild-type strain. Overall, these results describe a pathway, which is used by S. coelicolor to catabolize tryptophan and that could be inactivated to increase antibiotic production.

show abstract

Gene expression of enzymes for tryptophan degradation pathway is upregulated in the skin lesions of patients with atopic dermatitis or psoriasis

Cited by 42 publications

References 25 publications

Adult Human Fibroblasts Are Potent Immunoregulatory Cells and Functionally Equivalent to Mesenchymal Stem Cells

Adult Human Fibroblasts Are Potent Immunoregulatory Cells and Functionally Equivalent to Mesenchymal Stem Cells

Mouse Models for Atopic Dermatitis Developed in Japan

Tryptophan catabolism via kynurenine production in Streptomyces coelicolor: identification of three genes coding for the enzymes of tryptophan to anthranilate pathway

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