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Neuropeptide substance P and the immune response

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Abstract

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of the activity of immune cells. This review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immunobiology of substance P and discuss the clinical implications of its ability to modulate the immune response.

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Acknowledgments

CP was supported by grants from the National Institute of Health (R01 DK047343, and P30 DK 41301). The work in the RD laboratory was supported by the National Institute of Health (EY020889 and EY012963). We thank Dr. Susanne Leeman, Dr. Susanne Eiglmeier, and Dr. Ilya Leskov for their helpful comments on our manuscript.

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    Authors and Affiliations

    1. Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, 02114, USA

      Alireza Mashaghi, Anna Marmalidou, Mohsen Tehrani & Reza Dana

    2. Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, 80309, USA

      Peter M. Grace

    3. Division of Digestive Diseases, David Geffen School of Medicine, Inflammatory Bowel Disease Center, University of California, Los Angeles, Los Angeles, CA, USA

      Charalabos Pothoulakis

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    1. Alireza Mashaghi
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    Correspondence to Reza Dana.

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    A. Mashaghi and A. Marmalidou contributed equally to this work.

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    Mashaghi, A., Marmalidou, A., Tehrani, M. et al. Neuropeptide substance P and the immune response. Cell. Mol. Life Sci. 73, 4249–4264 (2016). https://doi.org/10.1007/s00018-016-2293-z

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