Semaphorin-3A: a promising therapeutic tool in allergic rhinitis

• Published in: Immunologic research 2022-04, Vol.70 (2), p.135-142
• Main Authors: Lotfi, Ramin, Zamanimehr, Nahid
• Format: Article
• Language: English
• Subjects: Allergic diseases; Allergic rhinitis; Allergies; Allergology; Animal models; Animals; Autoimmunity; Biomedical and Life Sciences; Biomedicine; Cell proliferation; Dendritic cells; Foxp3 protein; Health services; Helper cells; Humans; Hypersensitivity; Immune response; Immune system; Immunology; Inflammatory diseases; Internal Medicine; Lymphocytes; Lymphocytes T; Medicine/Public Health; Mice; Mucosa; Neuropilin; Neuropilin-1; Pathogenesis; Patients; Proteins; Receptors; Review; Rhinitis; Rhinitis, Allergic - drug therapy; Semaphorin-3A - metabolism; Semaphorin-3A - pharmacology; Signal Transduction; T-Lymphocytes, Regulatory
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-022-09264-1

Semaphorin-3A (Sema-3A), a secreted member of the semaphorin family, is well known for playing regulatory functions at all stages of the immune response. Sema-3A transduces signals by binding to its cognate receptors, namely, class A plexins (Plxns A1 to A4) and neuropilin-1 (Nrp-1). The downstream diverse signaling pathways induced by connecting Sema-3A to its receptors were found to be involved in the pathogenesis of different immunological disorders, ranging from cancer to autoimmunity and allergies. Recent studies have demonstrated that Sema-3A expression is diminished in the murine models and patients with allergic rhinitis (AR; a chronic inflammatory disorder of the nasal mucosa), suggesting the involvement of Sema-3A in AR pathogenesis. Investigations also revealed that treatment of these mice with exogenous Sema-3A protein alleviates the clinical symptom scores of AR, thereby compensating for the reduced expression of Sema-3A in AR. Indeed, Sema-3A treatment could suppress allergic responses in AR via inhibiting Th2/Th17 responses and boosting Th1/Treg responses. Also, Sema-3A could diminish dendritic cell (DC) maturation and T cell proliferation. Since it is implicated in the pathogenesis of AR; thus, Sema-3A turns to be a promising tool of therapy to be studied and utilized in this disease. This review intends to highlight the recent evidence on the role of Sema-3A in AR pathogenesis and summarizes the recent findings regarding the expression status of Sema-3A, as well as its therapeutic potential for treating this disease. Highlights Sema-3A plays regulatory functions at all stages of the immune response. Sema-3A receptors are the class A plexins (A1-A4) and neuropilin-1 (Nrp-1). Sema-3A expression is reduced in murine models and patients with allergic rhinitis. Connecting Sema-3A to Nrp-1 increases Foxp3 expression in Treg cells. Injecting Sema-3A protein exerts therapeutic effects in mouse models of allergic diseases. Sema-3A shows promise as a therapeutic tool for the treatment of allergic rhinitis.