C5a enhances Vδ1 T cells recruitment via the CCL2-CCR2 axis in IgA nephropathy.

BACKGROUND: Mucosal immune-associated γδ T cells have been implicated in IgA nephropathy (IgAN). However, the involvement of Vδ1 T cells, the major γδ T cells subtype, in renal damage and the mechanism underlying their migration from peripheral blood to kidney in IgAN remain unclear. METHODS: Clinical data from IgAN patients and healthy controls (HC) were analyzed. Phenotypes and chemokine receptors of γδ T cell were compared between IgAN patients and HC. Immunohistochemistry and immunofluorescence were performed to assess the infiltration of γδ T cell subsets and the expression of chemokine in renal tissues. In vitro, C5a was used to stimulate the human glomerular mesangial cells (HMCs) and chemotaxis experiment was used to examine Vδ1 T cells migration. Correlation between Vδ1 T cells and related clinical indicators were analyzed. RESULTS: IgAN patients exhibited decreased Vδ1 T cell in blood but increased levels in kidneys compared to HC. Increased CCR2-expressing Vδ1 T cells and serum level of CCL2 were observed in IgAN patients. CCL2 co-localized with CCR2 in HMCs of IgAN. In vitro, C5a enhanced Vδ1 T cells recruitment by HMCs through CCL2-CCR2 axis. Importantly, circulating Vδ1 T cell levels showed a negatively correlated with both the urinary protein creatinine ratio (UACR) and 24-hour urine protein (UP). Moreover, kidney infiltration of Vδ1 cells positively correlated with UACR, UP, mesangial hyperplasia and renal tubule atrophy/interstitial fibrosis in IgAN. CONCLUSIONS: C5a-induced production of CCL2 by HMCs facilitates Vδ1 T cells recruitment via the CCL2-CCR2 axis, contributing to renal damage in IgAN.

Distribution and functions of γδ T cells infiltrated in the ovarian cancer microenvironment.

BACKGROUND: The role of γδ T cells, innate-like lymphocytes with unrestrained MHC, in various malignancies has recently been extensively studied. However, there is limited research regarding γδ T cells in ovarian cancer (OC) patients. METHODS: Here, we investigated the distribution patterns of γδ T cells and their main subsets in peripheral blood and tumor tissues among OC patients, benign ovarian tumor (BOT) patients, and age-matched healthy controls (HC) by flow cytometry, as well as the expression levels of IFN-γ and IL-17A secreted from γδ T cells. Immunohistochemical staining was utilized to detect the numbers of γδ T cells and their main subsets in different types of ovarian tumor tissues. Additionally, we also investigated chemotaxis effects on γδ T cells, as well as their cytotoxic activity and proliferation. RESULTS: We found that the percentages of γδ T cells and Vδ1 T cells were significantly higher in OC tissues than BOT tissues and normal (N) ovarian tissues, while there were no obvious differences in peripheral blood. Meanwhile, higher numbers of γδ T cells and Vδ1 T cells were observed in OC tissues, and were positively related to advanced clinicopathological features of OC patients. Further, the levels of IFN-γ secreted by γδ T cells were relatively lower, while IL-17A was expressed at a high level in both the peripheral blood and tissues of OC patients. Chemotaxis assay revealed that supernatants derived from OC tissues possessed a stronger capacity to attract and recruit γδ T cells. However, γδ T cells sorted from OC tissues showed weakened cytotoxic activity against ovarian cancer cells, and γδ T cells cocultured with OC tissue supernatants could effectively inhibit the proliferative activity of naïve CD4+ T cells. CONCLUSIONS: These data suggested that γδ T cells might have critical roles in OC progression and potential utilization in treatment approaches or prognosis prediction.