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

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.

Gut Inflammation in Axial Spondyloarthritis Patients is Characterized by a Marked Type 17 Skewed Mucosal Innate‐like T Cell Signature

“…Various reports have demonstrated a recruitment of innate‐like T cells to the site of inflammation in chronic inflammatory diseases, such as the synovial fluid in SpA (5) and the inflamed intestine in IBD (6,7). In line with these, these cells have been ascribed effector roles in several arthritis and colitis animal models, as demonstrated by reduced disease severity in γδ‐T and MAIT cell knockout mice (8–10). Importantly, innate‐like T cells show plasticity and can be skewed to a proinflammatory state during disease.…”

Role of neutrophil interleukin-23 in spondyloarthropathy spectrum disorders

“…Indeed, as previously mentioned, neutrophilderived NE is known to induce TNFα production from γδ T-cells through PAR1 stimulation (44). Interestingly, in a murine model of psoriatic arthritis, γδ T-cells have been shown to regulate neutrophil expansion and recruitment to sites of inflammation, which may allow a neutrophil-γδ T-cell feedback loop to establish at such sites (72).…”

Immune Regulatory Networks and Therapy of γδ T Cells in Liver Cancer: Recent Trends and Advancements

“…Peripheral γδ T cells limit the expansion and recruitment of neutrophils to alleviate inflammation. 66 , 67 In a liver ischemia–reperfusion injury model, γδ TCR and IL-17a contribute to the increase in neutrophil numbers and exacerbate liver injury. 68 It is thus clear that the relationships between γδ T cells and other immune cells are extensive and far-reaching, shaping the body’s vast immune regulatory network.…”