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  • Review Article
  • Published:

Immunological functions of the neuropilins and plexins as receptors for semaphorins

Key Points

  • Cumulative evidence indicates that semaphorins, which were originally identified as axon-guidance molecules, participate in immune responses.

  • Two groups of proteins, the neuropilins and plexins, have been identified as the main semaphorin receptors.

  • Neuropilin 1 has been shown to be a regulatory T (TReg) cell marker and to be involved in the functions of TReg cells.

  • Plexin-mediated signals have been elucidated in both immune and bone systems.

  • Semaphorins and their receptors have been implicated in various immune disorders, such as multiple sclerosis, rheumatoid arthritis and allergy.

  • Semaphorins and their receptors are potential therapeutic targets and diagnostic markers for various diseases.

Abstract

Semaphorins were originally identified as axon-guidance molecules that function during neuronal development. However, cumulative evidence indicates that semaphorins also participate in immune responses, both physiological and pathological, and they are now considered to be potential diagnostic and/or therapeutic targets for a range of diseases. The primary receptors for semaphorins are neuropilins and plexins, which have cell type-specific patterns of expression and are involved in multiple signalling responses. In this Review, we focus on the roles of neuropilin 1 (NRP1) and plexins in the regulation of the immune system, and we summarize recent advances in our understanding of their pathological implications.

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Figure 1: The structure of and interactions between semaphorins and their receptors.
Figure 2: The structure and binding sites of neuropilins.
Figure 3: Effects of semaphorins on integrin function.
Figure 4: Plexin A1- and plexin B1-mediated signalling in bone homeostasis.

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Acknowledgements

We gratefully thank S. Kang, K. Morimoto, S. Nojima and H. Yoshida for help with the figures and tables. This study was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to A.K. and H. K.), and by the Funding Programs for Core Research for Evolutional Science and Technology (to A.K.).

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Kumanogoh, A., Kikutani, H. Immunological functions of the neuropilins and plexins as receptors for semaphorins. Nat Rev Immunol 13, 802–814 (2013). https://doi.org/10.1038/nri3545

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