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Double-negative T cells ameliorate psoriasis by selectively inhibition on IL-17A producing γδ T cells

ABSTRACT: Psoriasis is a chronic immune-mediated skin condition influenced by genetics and environmental factors. γδ T cells, as the main sources of IL-17A, play pivotal roles in the inflammatory processes of psoriasis. During psoriasis pathogenesis, inhibiting the secretion of IL-17A has emerged as a novel therapeutic approach for treating psoriasis. Double-negative T (DNT) cells is a novel type of immunosuppressive cells. Our preliminary research has unveiled that DNT cells play a significant immunoregulatory role in autoimmune and allergic diseases. In this study, we aimed to evaluate the protection of DNT cells and explore its underlying mechanism.

ORGANISM(S): Mus musculus

PROVIDER: GSE248626 | GEO | 2024/04/10

REPOSITORIES: GEO

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D-mannose suppressed γδ T cells and alleviated murine psoriasis.

Project description:Psoriasis is a chronic skin suffering with multiple comorbidities such as psoriatic arthritis and cardiovascular diseases. Increasing evidences have shown the γδ T cells as the sources of IL-17A play critical roles in the psoriatic syndrome. However, there is still lack an effective way to manipulate these pathogenic γδ T cells which were less studied relative to ab T cells. The present study aims to characterize the phenotype of γδ T cells and evaluate the impact of D-mannose (a C-2 epimer of glucose) on γδ T-mediated psoriasis. We found the psoriatic γδ T cells underwent robust proliferation and acquired an IL-17 producing phenotype. The transcriptomic profiles of these skin draining LN γδ T cells had elevated glycolytic features. Importantly, Treatment of D-mannose inhibited γδ T cells and successfully alleviated the local and systematic inflammations induced by imiquimod. The decreased AKT/mTOR/HIF-1a signaling and glycolytic ability may contribute to the suppression of γδ T cells achieved by mannose. Our study deepened the understandings of γδ T cells in psoriasis, meanwhile, promoted D-mannose utilization as a potent clinical application for γδ T cells driven autoimmune diseases.

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IL-17A plays a central role in the expression of psoriasis signature genes through induction of IkappaB-zeta in keratinocytes

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IL-17A plays a central role in the expression of psoriasis signature genes through induction of IkappaB-zeta in keratinocytes

2016-03-08 | GSE77719 | GEO

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