Dataset Information

Mast cells express IL17A, IL17F and RORC, are activated and persist with IL-17 production in resolved skin of patients with chronic plaque-type psoriasis.

ABSTRACT: Little is known about IL-17 expression in psoriasis and the actual cellular source of IL-17 remains incompletely defined. We show that high numbers of IL-17 + mast cells persisted in resolved lesions after treatment (anti-IL-17A, anti-IL-23, UVB or topical dithranol) and correlated inversely with the time span in remission. IL-17 + mast cells were found in T cell-rich areas and often close to resident memory T cells (T_rm) in active psoriasis and resolved lesional skin. Digital cytometry by deconvolution of RNA-seq data showed that activated mast cells were increased in psoriatic skin, while resting mast cells were almost absent and both returned to normal levels after treatment. When primary human skin mast cells were stimulated with T cell cytokines (TNFα, IL-22 and IFNγ), they responded by releasing more IL-17A, as measured by ELISA. In situ mRNA detection using padlock probes specific for transcript variants of IL17A, IL17F, and RORC (encoding the Th17 transcription factor RORγt) revealed positive mRNA signals for IL17A, IL17F, and RORCin tryptase + cells, demonstrating that mast cells have the transcriptional machinery to actively produce IL-17. Mast cells thus belong to the center of the IL-23/IL-17 axis and high numbers of IL-17 + mast cells predict an earlier disease recurrence.

SUBMITTER: Benezeder T

PROVIDER: S-EPMC10896398 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Mast cells express IL17A, IL17F and RORC, are activated and persist with IL-17 production in resolved skin of patients with chronic plaque-type psoriasis.

Benezeder Theresa T Bordag Natalie N Woltsche Johannes J Teufelberger Andrea A Perchthaler Isabella I Weger Wolfgang W Salmhofer Wolfgang W Gruber-Wackernagel Alexandra A Painsi Clemens C Zhan Qian Q El-Heliebi Amin A Babina Magda M Clark Rachael R Wolf Peter P

Research square 20240216

Little is known about IL-17 expression in psoriasis and the actual cellular source of IL-17 remains incompletely defined. We show that high numbers of IL-17 + mast cells persisted in resolved lesions after treatment (anti-IL-17A, anti-IL-23, UVB or topical dithranol) and correlated inversely with the time span in remission. IL-17 + mast cells were found in T cell-rich areas and often close to resident memory T cells (T<sub>rm</sub>) in active psoriasis and resolved lesional skin. Digital cytomet ...[more]

PMID: 38410434

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Project description:BackgroundInterleukin 17 is a proinflammatory cytokine involved in immune response after allograft transplantation. IL-17 family of proinflammatory cytokines includes IL-17A and IL-17F. Previous studies have demonstrated that the rs2275913 IL17A and the rs11465553 IL17F gene polymorphism are associated with kidney allograft function. Because of the association between these polymorphisms and post-transplant immune response, we assume that these single nucleotide polymorphisms may affect morphological structure of transplanted kidney. The aim of this study was to examine the association of rs2275913 IL17A and rs2397084, rs11465553 and rs763780 IL17F gene polymorphisms with histopathological changes in transplanted kidney biopsies such as: glomerulitis, tubulitis, arteritis, cell infilitration and fibrosis.MethodsThe study enrolled 82 patients after renal graft transplantation in whom a kidney biopsy was performed because of impaired graft function. The rs2397084 T > C (Glu126Gly), rs11465553 G > A (Val155Ile) and rs763780 T > C (His167Arg) polymorphisms within the IL17F gene and the rs2275913 A > G (- 197 A > G) polymorphism within the IL17A gene promoter were genotyped using TaqMan genotyping assays on a 7500 FAST Real-Time PCR System (Applied Biosystems, USA).ResultsThere was a significant association between the rs2275913 IL17A gene polymorphism and the grade of tubulitis, which was more severe among patients with the A allele, compared to recipients with the GG genotype (GG vs. AG + AA, P = 0.02), and with the grade of arteriolar hyaline thickening and mesangial matrix increase, which were more severe among patients with the G allele compared to recipients with the AA genotype (AA vs. AG + GG, P = 0.01 and P = 0.04, respectively). Tubular atrophy and interstitial fibrosis were more severe among individuals with the C allele at the rs763780 IL17F gene polymorphism (TT vs. TC, P = 0.09 and P = 0.017, respectively). However, it should be taken into account that the statistical significance was achieved without correction for multiple testing, and no significant association would remain significant after such correction.ConclusionsThe results of this study may suggest a possible association between the rs2275913 IL17A and rs2275913 IL17A gene polymorphisms and some histopathological changes in transplanted kidney biopsies.

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Dataset Information

Mast cells express IL17A, IL17F and RORC, are activated and persist with IL-17 production in resolved skin of patients with chronic plaque-type psoriasis.

Publications

Mast cells express IL17A, IL17F and RORC, are activated and persist with IL-17 production in resolved skin of patients with chronic plaque-type psoriasis.

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