Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: γδ T cells are non-conventional lymphocytes that straddle between innate and adaptive immunity. Although γδ T cells have been implicated in psoriatic arthritis, the exact mechanisms that govern pathogenicity remain elusive.
Methods: To investigate the roles of γδ T cells in eliciting psoriatic arthritis-like pathology, we performed in vivo gene transfer of IL-23 (minicircle DNA) in B10.RIII (WT) and/or TCRδ-/- mice. qRT-PCR, RNAseq, Western blot, flow cytometry, ELISA, H&E and immunofluorescence staining were used to analyze the phenotype of WT and transgenic mice in this study.
Results: Herein, we show that IL-23 MC gene transfer induces SCART scavenger receptors 1/2 surface marker of adult γδ T cells and a population of CD11b+LY6G+ associated with synovitis and epidermal hyperplasia in joint and skin tissues respectively which is accompanied with onycholysis and enthesitis hallmark pathologic features of human PsA. We observed a profound neutrophil inflammatory infiltrate in the synovium, epidermis, nail bed, and enthesis in IL-23 gene transfer WT mice, which were absent in TCRδ-/- mice. Furthermore, our data demonstrate that absence of γδ T cells was associated with an attenuation of inflammatory gene expression as well as expression of neutrophil markers which mechanistically correlated with a reduction of IL-17A and a marked increase of the anti-inflammatory cytokine IL-27.
Conclusion: Collectively, our data demonstrate that γδ T cells are critical components in pathogenesis of IL-23-induced psoriatic arthritis like disease, suggesting that γδ T cells could be potentially targeted for treatment of the rheumatic diseases.
To cite this abstract in AMA style:Nguyen C, Chan T, Tagkopoulos I, Eberl M, Adamopoulos I. Genetic Ablation of γδTCR Inhibits IL-23-induced Neutrophilia and Attenuates Epidermal Hyperplasia, Synovitis, Onycholysis and Enthesitis Associated with Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/genetic-ablation-of-%ce%b3%ce%b4tcr-inhibits-il-23-induced-neutrophilia-and-attenuates-epidermal-hyperplasia-synovitis-onycholysis-and-enthesitis-associated-with-psoriatic-arthritis/. Accessed April 13, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/genetic-ablation-of-%ce%b3%ce%b4tcr-inhibits-il-23-induced-neutrophilia-and-attenuates-epidermal-hyperplasia-synovitis-onycholysis-and-enthesitis-associated-with-psoriatic-arthritis/