Semaphorin3A: A potential therapeutic tool in immune-mediated diseases

Abstract

The significance of semaphorin3A (sema3A) in regulating immune-mediated inflammation is widely reported. There are multiple mechanisms involved in the process of sema3A-mediated regulation. One of them is the ability of sema3A to maintain a sufficient regulation of both T-cell and B-cell activation. Because it is involved in the pathogenesis of many autoimmune, infectious, and malignant diseases, sema3A turns to be a promising therapeutic tool to be studied and applied in these diseases. Keywords: Semaphorin 3A, immune mediated diseases, atopic diseases the other, it increased the serum level of the anti-inflammatory cytokine IL-10 (11). In line with these findings, sema3A expression was found to be decreased on CD4 + T cells of RA patients, whereas NP-1 expression on these cells was increased. CD4+NP-1+T cells, known as T regulatory cells and a source of IL-10, were reported to be decreased in RA. In this case, the addition of sema3A into a co-culture with T cells acts directly on CD4+NP-1+T cells and increases IL-10 production, supporting its therapeutic beneficial effect in RA (11). In a recent study, the expression of sema3A in synovial tissues of RA patients was investigated. Disease activity and the histological features of synovial tissues were also assessed in relation to sema3A expression. Human synovial tissues were obtained from established RA patients, compared those of patients suffering from osteoarthritis (OA), and assessed for sema3A, VEGF-A, and NP-1mRNA expression, using quantitative real-time polymerase chain reaction (qPCR). The protein expression of sema3A in synovial lining cells was decreased in RA tissues compared with that in OA samples. Sema3A mRNA levels correlated with the inflammation score, namely with the extent of lymphocyte infiltration (R=0.50, p=0.004). Thus, the correlation of sema3A expression in RA synovial tissues may become a therapeutic target in RA (12).Semaphorin3A and systemic lupus erythematosus (SLE): Hypothesizing that sema3A may have a similar role in SLE, we assessed its serum levels in SLE patients. Sema3A serum levels in SLE patients were found to be significantly lower than in RA patients (55.04±16.30 ng/mL vs. 65.54±14.82 ng/mL, p=0.018) and lower yet than in normal individuals (55.04±16.30 ng/ mL vs. 74.41±17.60 ng/mL, p<0.0001). Serum sema3A levels in SLE patients were low in negative correlation with SLE disease activity, renal damage, and the presence of relevant autoantibodies (R= −0.89, p<0.0001) (13). Being the source of autoantibodies and pro-inflammatory cytokines, the regulatory status of B cells was evaluated. The expression of sema3A on B regulatory (Breg) cells, namely CD19 + CD25high and NP-1 + was analyzed. As expected sema3A expression on these cells was significantly lower in SLE patients when compared to B cells from normal individuals, suggesting this to be in part responsible for B-cell auto-reactivity in SLE. Our other finding was the down-regulation of NP-1 expression on B cells from SLE patients, suggesting that both sema3A and N...

The Role of microRNAs in the Cisplatin- and Radio-Resistance of Cervical Cancer

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Activity‐induced secretion of semaphorin 3A mediates learning

“…The semaphorin family has attracted much attention in various biological fields, including neuroscience, immunology, and oncology (Gurrapu et al., 2018; Kolodkin & Tessier‐Lavigne, 2011; Vadasz & Toubi, 2018). In neuroscience, semaphorins have been intensively studied in terms of axon guidance and cell migration.…”

The Role of Semaphorins and Their Receptors in Innate Immune Responses and Clinical Diseases of Acute Inflammation

“…Although semaphorins were originally identified for their involvement in neural guidance and development, they have since been found to have important roles in many pathophysiological processes. Work over the past 20 years has demonstrated the function of semaphorins and their receptors in numerous diseases including cancer (28)(29)(30)(31), disorders of bone turnover (32)(33)(34)(35)(36)(37), angiogenesis (38)(39)(40)(41)(42), autoimmune and rheumatologic diseases (43)(44)(45)(46)(47)(48)(49)(50), and inflammatory conditions. In this Review, we summarize the rapidly evolving literature on the functional roles of immune semaphorins at a cellular and intercellular level, and discuss their pathogenic roles and therapeutic implications in acute inflammatory diseases and in the innate immune response.…”