IDO-expressing Fibroblasts Suppress the Development of Imiquimod-induced Psoriasis-like Dermatitis

Elizei, Sanam Salimi; Pakyari, Mohammadreza; Ghoreishi, Mehran; Kilani, Ruhangiz T.; Mahmoudi, Sanaz; Ghahary, Aziz

doi:10.1177/0963689718757482

Cited by 5 publications

(2 citation statements)

References 29 publications

(39 reference statements)

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“…Thus, IDO1-overexpressing fibroblasts have been demonstrated to suppress the development of skin lesions in this same IMQ-induced mouse model of psoriasis. 20 In addition, Kim et al 21 determined that manipulations that increase reactive oxygen species result in the amelioration of psoriasiform lesion development in response to IMQ by upregulating IDO expression and enhancing Treg function. Furthermore, IDO, possibly IDO1, is upregulated in psoriasis lesions.…”

Section: Discussionmentioning

confidence: 99%

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

Choudhary

Ajebo

Uaratanawong

et al. 2022

Int J�Tryptophan�Res

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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.

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Section: Discussionmentioning

confidence: 99%

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

Choudhary

Ajebo

Uaratanawong

et al. 2022

Int J�Tryptophan�Res

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“…The intra-lesional injection of IDO1-expressing fibroblasts in IMQ-induced psoriasislike dermatitis significantly improves the clinical lesional appearance and reduces the infiltration of IL-17 and IL-23 by lymphocytes and DCs, respectively [126]. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity [127].…”

Section: Endogenous L-tryptophan-derived Ahr Ligandsmentioning

confidence: 99%

Role of AHR Ligands in Skin Homeostasis and Cutaneous Inflammation

Fernández‐Gallego

Sánchez‐Madrid

Cibrián

2021

Cells

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Aryl hydrocarbon receptor (AHR) is an important regulator of skin barrier function. It also controls immune-mediated skin responses. The AHR modulates various physiological functions by acting as a sensor that mediates environment–cell interactions, particularly during immune and inflammatory responses. Diverse experimental systems have been used to assess the AHR’s role in skin inflammation, including in vitro assays of keratinocyte stimulation and murine models of psoriasis and atopic dermatitis. Similar approaches have addressed the role of AHR ligands, e.g., TCDD, FICZ, and microbiota-derived metabolites, in skin homeostasis and pathology. Tapinarof is a novel AHR-modulating agent that inhibits skin inflammation and enhances skin barrier function. The topical application of tapinarof is being evaluated in clinical trials to treat psoriasis and atopic dermatitis. In the present review, we summarize the effects of natural and synthetic AHR ligands in keratinocytes and inflammatory cells, and their relevance in normal skin homeostasis and cutaneous inflammatory diseases.

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Immunometabolic Approaches Mitigating Foreign Body Response and Transcriptome Characterization of the Foreign Body Capsule

Macias,

Palmer,

Simonovich

et al. 2024

Adv Healthcare Materials

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Directing immunometabolism presents new opportunities to modulate key cell types associated with the formation of foreign body response (FBR) capsule. Contrasting approaches directing immunometabolism are investigated to mitigate FBR: a broadly suppressive metabolic inhibitor (MI) cocktail comprised of 2‐deoxyglucose (2‐DG), metformin, and 6‐diazo‐5‐oxo‐l‐norleucine (DON) with daily systemic dosing regimen, and local weekly injection of the more narrowly focused tryptophan catabolizing IDO‐Gal3 fusion protein. Treatments significantly decrease FBR capsule formed around subcutaneously implanted cellulose disks. MI cocktail results in a substantially thinner FBR capsule (40% of control), while weekly local injection of IDO‐Gal3 also results in a thinner FBR capsule (69% of control). RNA‐sequencing capsule transcripts reveal MI cocktail promotes quiescence, with decreased antigen processing and presentation, T helper subset differentiation, and cytokine‐cytokine receptor pathway. IDO‐Gal3 promotes pro‐regenerative, alternatively activated M2‐like macrophages and T helper 2 cells, with increased expression of type 2 response‐associated genes (Il4, Il13, Arg1, Mrc1, Chil3, Gata3). IDO‐Gal3 decreases pro‐inflammatory innate sensing pathways, and C‐type lectin receptor, NOD‐like receptor, RIG‐I‐like receptor, and Toll‐like receptor signaling. This work helps define key gene targets and pathways concomitantly regulated in the FBR capsule during immunometabolic modulation compared to control FBR capsule.

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IDO-expressing Fibroblasts Suppress the Development of Imiquimod-induced Psoriasis-like Dermatitis

Cited by 5 publications

References 29 publications

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

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

Role of AHR Ligands in Skin Homeostasis and Cutaneous Inflammation

Immunometabolic Approaches Mitigating Foreign Body Response and Transcriptome Characterization of the Foreign Body Capsule

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