Peripheral gamma delta T Cells Regulate Neutrophil Expansion and Recruitment in Experimental Psoriatic Arthritis

Objective This study was undertaken to identify the mechanistic role of gamma delta 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 delta-deficient (TCR delta(-/-)) 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 gamma delta T cells. Results We demonstrated that gamma delta T cells support systemic granulopoiesis, which is critical for murine PsA-like pathology. Briefly, gamma delta 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 TCR delta(-/-) mice, no GM-CSF+/IL-17A+ gamma delta T cells were detected locally in the inflamed skin or bone marrow in WT mice. Our data showed that nonresident gamma delta 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 gamma delta T cells initiate the disease but demonstrate a novel role of gamma delta T cells in neutrophil regulation that can be exploited therapeutically in PsA patients.