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

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Abstract

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.

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Abbreviations

AR:

Allergic rhinitis

Sema-3A:

Semaphorin-3A

Plxns:

Plexins

Nrp-1:

Neuropilin-1

Treg cell:

Regulatory T cell

Foxp3:

Forkhead box p3

DC:

Dendritic cell

IL-4:

Interleukin-4

IFN-γ:

Interferon-γ

IgE:

Immunoglobulin E

I.N.:

Intranasal

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Acknowledgements

The authors would like to thank the Clinical Research Development Center of Tohid Hospital, for all their support and guidance during carrying out this study.

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Authors and Affiliations

  1. Clinical Research Development Center, Tohid Hospital, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Ramin Lotfi & Nahid Zamanimehr

  2. Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, 6617713446, Sanandaj, Iran

    Ramin Lotfi

  3. Department of Emergency Medicine, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Nahid Zamanimehr

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Lotfi, R., Zamanimehr, N. Semaphorin-3A: a promising therapeutic tool in allergic rhinitis. Immunol Res 70, 135–142 (2022). https://doi.org/10.1007/s12026-022-09264-1

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