Signalling of multiple interleukin (IL)‐17 family cytokines via IL‐17 receptor A drives psoriasis‐related inflammatory pathways

Tollenaere, Maxim A. X.; Hebsgaard, Josephine B.; Ewald, David Adrian; Lovato, Paola; Garcet, Sandra; Li, X; Pilger, Steven; Tiirikainen, Minna Lund; Bertelsen, Malene; Krueger, James G.; Norsgaard, Hanne

doi:10.1111/bjd.20090

Cited by 35 publications

(35 citation statements)

References 35 publications

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“…cytometry was impossible due to the pre-stimulation with PMA/ionomycin. The current hypothesis is further supported by Tollenaere et al, who observed the existence of few Th17 cells in human psoriatic skin lesions which produced high levels of IL-17 cytokines (22).…”

Section: Discussionsupporting

confidence: 73%

Psoriasis-like Inflammation Induced in an Air-pouch Mouse Model

Charitidis

Damlund

Koch

2021

In Vivo

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Background/Aim: The pathway of initiation of psoriasis comprises the differentiation and infiltration of Thelper 17 (Th17) cells into the skin, characterized by the production of interleukin 17A and 17F (IL-17A/IL-17F) among other cytokines, resulting in a downstream cascade of events. Due to the lack of simplicity in psoriasis models, we aimed to develop an easily and rapidly inducible mouse model for the IL-23/IL-17 pathway with quick readouts from a straightforward lavaging process and with detectable cytokine levels. Materials and Methods: We utilized the 6-day airpouch mouse model, injected with a combination of anti-CD3, IL-23 and L-1β. At 24, 48 and 72 h, intra-pouch secretion of IL-17A, IL-17F and C-X-C motif chemokine ligand 1 were measured Skin biopsies were collected and immune cell infiltration evaluated, and intra-pouch immune cells were isolated and analyzed. Results: The combination of anti-CD3, IL-23 with and without IL-1 significantly increased intrapouch levels of IL-17A/IL-17F at 24 and 72 h, triggering a downstream production of C-X-C motif chemokine ligand 1. The cytokines were detectable even 72 h post-induction. T-cell receptor beta was down-regulated on CD4 + and CD8 + T-cells, indicating intra-pouch T-cell activation. Αnti-CD3 induced CD3+ cell migration into the subcutis and the lining tissue surrounding the cavity of the air pouch, where in the latter, a similar distribution pattern of Il17a mRNA-expressing cells was also observed. However, no Th17 cell differentiation nor changes in IL-17A + granulocytes were observed. Conclusion: The induced air-pouch mouse model induced with a cocktail of anti-CD3, IL-23 with or without IL-1β is able to mirror the IL-23/IL-17 axis of psoriasis-like inflammation characterized by immune cell infiltration and cytokine secretion.

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Section: Discussionsupporting

confidence: 73%

Psoriasis-like Inflammation Induced in an Air-pouch Mouse Model

Charitidis

Damlund

Koch

2021

In Vivo

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“…One of the key cytokines in psoriasis is IL‐17A, as evidenced by the high efficacy of monoclonal antibodies targeting IL‐17A or its receptor IL‐17RA for the treatment of patients with psoriasis 4 . IL‐17A signals through a receptor complex that includes IL‐17RA and IL‐17RC 5 . While IL‐17RA is expressed on multiple cell types, IL‐17RC is expressed mainly on epithelial cells 6 .…”

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confidence: 99%

“…4 IL-17A signals through a receptor complex that includes IL-17RA and IL-17RC. 5 While IL-17RA is expressed on multiple cell types, IL-17RC is expressed mainly on epithelial cells. 6 In the skin, the main target cells for IL-17A are the keratinocytes, in which IL-17A signalling leads to activation of innate immune responses with the induction of antimicrobial peptides, cytokines and chemoattractants through the activation of the nuclear factor kappa B (NF-jB), p38-MAPK, C/EBP-b and other pathways.…”

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confidence: 99%

miR ‐378a regulates keratinocyte responsiveness to interleukin‐17A in psoriasis*

et al. 2022

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“…Interleukin-17 is a pro-inflammatory cytokine produced by the T helper 17 (Th17) cells and plays an important role in the development and progression of inflammatory and autoimmune diseases [ 38 ]. Mechanisms underlying the complex pathogenesis of psoriasis have not been fully understood, but there is increasing evidence that the IL-17/IL-23 axis plays a crucial role in the inflammatory response in psoriasis [ 39 , 40 ]. The vitamin D 3 analogue calcipotriol used in treating psoriasis inhibited IL-23/IL-17 axis and neutrophil infiltration in psoriatic skin through the vitamin D receptor (VDR) in keratinocytes [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

TaaI/Cdx-2 AA Variant of VDR Defines the Response to Phototherapy amongst Patients with Psoriasis

Lesiak,

Wódz,

Ciążyńska

et al. 2021

Life

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1,25-dihydroxyvitamin-D3 plays a central role in the immune system via binding to the vitamin D receptor. VDR polymorphisms have been associated with multiple autoimmune disorders, including psoriasis. Until now, five VDR polymorphisms, FokI, ApaI, BsmI, TaqI and TaaI/Cdx2, have been studied in psoriasis, with contradicting results. Therefore, this study aimed to evaluate the association of VDR polymorphisms with susceptibility to psoriasis, effectiveness of NB-UVB phototherapy and concentration of proinflammatory cytokines and vitamin D amongst the Polish population. VDR polymorphisms were analyzed by PCR-RFLP or real-time PCR. We found that the frequency of the TaaI/Cdx-2 GG genotype was significantly higher in psoriasis patients and was associated with regulation of IL-17 and IL-23 concentration. Moreover, TaaI/Cdx-2 AA might have a significant effect on the response to phototherapy amongst patients with psoriasis. Our results suggest that VDR is a susceptibility factor for psoriasis development. Moreover, TaaI/Cdx-2 variants have a significant effect on the response to phototherapy amongst patients with psoriasis and regulation of inflammatory response via decrease of IL-17 and IL-23 level after UVB phototherapy in the Polish population. Results of our study provide some evidence in support of the hypothesis that the vitamin D signaling pathway may be of relevance for pathogenesis and treatment of psoriasis.

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Signalling of multiple interleukin (IL)‐17 family cytokines via IL‐17 receptor A drives psoriasis‐related inflammatory pathways

Abstract: The gene array dataset described in this publication has been deposited in NCBI's Gene Expression Omnibus and is accessible through GEO Series accession number GSE158448 (https://www.ncb i.nlm.nih.gov/geo/query/acc.cgi?acc= GSE158448).

Cited by 35 publications

References 35 publications

Psoriasis-like Inflammation Induced in an Air-pouch Mouse Model

Psoriasis-like Inflammation Induced in an Air-pouch Mouse Model

miR ‐378a regulates keratinocyte responsiveness to interleukin‐17A in psoriasis*

TaaI/Cdx-2 AA Variant of VDR Defines the Response to Phototherapy amongst Patients with Psoriasis

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