Peripheral γδ T Cells Regulate Neutrophil Expansion and Recruitment in Experimental Psoriatic Arthritis
Cuong Thach Nguyen, Hiroki Furuya, Dayasagar Das, Alina I. Marusina, Alexander A. Merleev, Resmi Ravindran, Zahra Jalali, Imran H. Khan, Emanual Maverakis, Iannis E. Adamopoulos
Abstract
Objective 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.