In:
Arthritis & Rheumatology, Wiley, Vol. 74, No. 9 ( 2022-09), p. 1524-1534
Abstract:
This study was undertaken to identify the mechanistic role of γδ T cells in the pathogenesis of experimental psoriatic arthritis (PsA). Methods In this study, we performed interleukin‐23 (IL‐23) gene transfer in wild‐type (WT) and T cell receptor δ–deficient (TCRδ −/− ) mice and conducted tissue phenotyping in the joint, skin, and nails to characterize the inflammatory infiltrate. We further performed detailed flow cytometry, immunofluorescence staining, RNA sequencing, T cell repertoire analysis, and in vitro T cell polarization assays to identify regulatory mechanisms of γδ T cells. Results We demonstrated that γδ T cells support systemic granulopoiesis, which is critical for murine PsA‐like pathology. Briefly, γδ T cell ablation inhibited the expression of neutrophil chemokines CXCL1 and CXCL2 and neutrophil CD11b+Ly6G+ accumulation in the aforementioned PsA‐related tissues. Although significantly reduced expression of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and IL‐17A was detected systemically in TCRδ −/− mice, no GM‐CSF+/IL‐17A+ γδ T cells were detected locally in the inflamed skin or bone marrow in WT mice. Our data showed that nonresident γδ T cells regulate the expansion of an CD11b+Ly6G+ neutrophil population and their recruitment to joint and skin tissues, where they develop hallmark pathologic features of human PsA. Conclusion Our findings do not support the notion that tissue‐resident γδ T cells initiate the disease but demonstrate a novel role of γδ T cells in neutrophil regulation that can be exploited therapeutically in PsA patients.
Type of Medium:
Online Resource
ISSN:
2326-5191
,
2326-5205
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2754614-7
Permalink
