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This article is part of the supplement: Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

Oral presentation

Regulation of immune cell responses by semaphorins and their receptors

Atsushi Kumanogoh12* and Hyota Takamatsu12

  • * Corresponding author: Atsushi Kumanogoh

Author Affiliations

1 Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Graduate School of Medicine Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan

2 World Premier International Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan

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Arthritis Research & Therapy 2012, 14(Suppl 1):O45  doi:10.1186/ar3600


The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/14/S1/O45


Published:9 February 2012

© 2012 Kumanogoh and Takamatsu; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called 'immune semaphorins', are crucially involved in various phases of immune responses (Figure 1) [1-3]. In addition, semaphorins and their receptors have been shown to be crucial for the pathogenesis of immunological disorders such as atopic dermatitis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis, These semaphorins regulate immune cell interactions during physiological and pathological immune responses. However, conventional static analysis could not determine definitively whether they regulate immune cell movement.

thumbnailFigure 1. Semaphorins are involved in physiological and pathological immune responses.

Materials and methods

Plexin-A1-/- mice were previously established [4]. Combinational studies, including imaging technique for visualizing single-cell dynamics and conventional immunological assays were performed.

Results and discussion

We find that plexin-A1-mediated semaphorin signals are crucially involved in the transmigration of DCs across the lymphatics to exit the periphery to induce antigen-specific T-cell priming using plexin-A1-/- mice. In addition, adoptive transfer experiments identify that Sema3A produced in the lymphatics functions as a ligand for the plexin-A1/NP-1 receptor complex expressed in DCs. Interestingly, plexin-A1 is localized at the trailing edge but not the leading edge of DCs during migration. Sema3A induces phosphorylation of the myosin light chain to promote actomyosin contraction, resulting in increased DC velocity in the constricted area (Figure 2). Collectively, these findings not only demonstrate the involvement of semaphorins in immune cell trafficking but also indicate that semaphorins are therapeutic targets to treat immunological disorders.

thumbnailFigure 2. Sema3A produced by the lymphatic induces actomyosin contraction during transmigration.

References

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    Nature 2007, 446:680-684. PubMed Abstract | Publisher Full Text OpenURL

  2. Suzuki K, et al.: Semaphorins and their receptors in immune cell interactions.

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  3. Nogi T, et al.: Structural basis for semaphorin signalling through the plexin receptor.

    Nature 2010, 467:1123-7. PubMed Abstract | Publisher Full Text OpenURL

  4. Takegahara N, et al.: Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis.

    Nat Cell Biol 2006, 8:615-622. PubMed Abstract | Publisher Full Text OpenURL

  5. Takamatsu H, et al.: Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II.

    Nat Immunol 2010, 11:594-600. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL