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Rheumatoid arthritis (RA) is a common autoimmune disease in which T helper-type 17 (Th17) cells have been critically involved. CD147 is a T cell activation-associated molecule and is involved in T cell development. However, it remains unclear whether CD147 participates in Th17 responses in RA patients. In this study, we demonstrated that in both the RA and healthy controls (HC) groups, CD147 expression on CD4+ T cells was increased in CCR6+ and CD161+ subsets, and was associated with IL-17 production. Ligation of CD147 with its monoclonal antibody (mAb) strongly inhibited Th17 responses, and knock down of CD147 expression on CD4+ Tm cells specifically enhanced Th17 responses, triggered by coculture with in vitro activated monocytes from HC. Further functional studies showed that anti-CD147 mAb decreased the activation of AKT, mTORC1 and STAT3 signaling, which is known to enhance Th17 responses. Ligation of CD147 with its mAb on CD4+ Tm cells specifically reduced Th17 responses induced by in vitro or in vivo activated monocytes from RA patients. In collagen-induced arthritis model, anti-CD147 mAb treatment reduced the Th17 levels and severity of arthritis in vivo. These data suggest that CD147 plays a negative role in regulating human Th17 responses. Anti-CD147 mAb can limit the extraordinary proliferation of Th17 cells and may be a new therapeutic option in RA. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory and angiogenic disease. This study aimed to explore the profiles of circulating angiogenic T cells (Tang cells) and the role of CD147 in Tang cell activation function in RA. Methods: Samples were obtained from patients with RA and health controls (HC). Then, Tang cells were quantified by flow cytometry (FCM) in the samples from 87 patients with RA and 29 HC. Tang cells were purified by magnetic cell sorting in cell culture–conditioned media, and the phosphorylation signals were determined by FCM. In addition, cytokine levels were assessed by enzyme-linked immunosorbent assay. Results: The percentage of circulating Tang cells increased and positively correlated with the number of endothelial progenitor cells in the RA group. Further, the percentage of Tang cells was closely related to disease activity, autoantibody positivity, and proangiogenic cytokine levels. Meanwhile, the expression of CD147 on Tang cells increased in patients with RA. CD147 participated in the Akt phosphorylation and VEGF level of the activated Tang cells. Conclusions: CD147 may play a critical role in regulating VEGF production of activated Tang cells by affecting Akt signaling, which in turn may serve an essential function in angiogenesis and RA pathogenesis. [ABSTRACT FROM AUTHOR]

Objective. Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis and increased cardiovascular risk. Angiogenic T cells (Tang), a specific T cell subset, have been identified and involved in the repair of damaged endothelium. This study aimed to analyze the Tang cell subsets in relation to disease specific features from SLE patients. Methods. Tang cell subsets were assessed in peripheral blood samples from 41 SLE patients and 22 healthy controls (HC) by flow cytometry on the basis of CD31 and CXCR4 expression on CD3+, CD4+, and CD8+ T cells. Results. The percentage of circulating CD8+CD31+CXCR4+ T cells (CD8+ Tang), but not CD3+CD31+CXCR4+ T cells (Tang) and CD4+CD31+CXCR4+ T cells (CD4+ Tang), in SLE was higher than HC. The percentages of Tang cell subsets in anti-dsDNA-positive SLE patients were significantly increased as compared to their negative counterparts and HC. Additionally, the levels of circulating Tang cell subsets were negatively correlated with age at sampling and at diagnosis, but not disease duration or disease activity. Conclusion. Anti-dsDNA-positivity may identify a group of SLE patients with increased Tang cell subsets and circulating CD8+ Tang cells may be viewed as a potentially useful biomarker of endothelial damage and cardiovascular risk in SLE. [ABSTRACT FROM AUTHOR]

Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3ζ and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4 + T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data indicate that CD147 and CD98 might play important roles in cyclophilin-induced cell migration. [ABSTRACT FROM AUTHOR]

• Tang cells and CD8+ Tang is elevated in SSc patients. • Anti-nucleolar pattern autoantibody may identify a higher risk of vasculopathy. • CD8+ Tang cells may serve as a useful characteristic of endothelial damage in SSc. • Tang and CD8+ Tang cells may serve as a surrogate characteristic of PAH and a therapeutic target for SSc patients. To ascertain the number and percentage of angiogenic T (Tang) cell subsets by flow cytometry in systemic sclerosis (SSc), and their relation with specific clinical features. Thirty SSc patients and 15 healthy controls (HCs) were included. Luminex was performed to analyze the levels of interleukin (IL)-17A, vascular endothelial growth factor (VEGF), tumor necrosis factor-α, and vascular cell adhesion molecule (VCAM). The ratio of circulating CD3 + CD31 + CXCR4 + T (CD3 + Tang) cells and CD8+ CD31 + CXCR4 + T (CD8+ Tang) cells in SSc patients was enlarger than in HCs, while CD4 + CD31 + CXCR4 + T cells (CD4 + Tang) exhibited no difference between SSc patients and HCs. The number and percentage of Tang cells were higher in SSc patients with pulmonary artery hypertension (PAH) than in non-PAH SSc patients and HCs. The ratios of Tang cell subsets in nucleolar pattern-positive SSc patients were markedly raised as compared with their negative ones and HCs. Additionally, the percentage of circulating CD3 + Tang cells was positively associated with VEGF serum levels in SSc patients. Meanwhile, the rate of CD8+ tang cells might have been emphatically corresponded to VEGF and VCAM serum levels in SSc patients. These results imply that the increase in Tang cells in peripheral blood are associated with immunoregulatory disturbances in SSc patients. [ABSTRACT FROM AUTHOR]