Riol-Blanco L, Ordovas-Montanes J, Perro M, Naval E, Thiriot A, Alvarez D, Paust S, Wood JN, von Andrian UH, et al.
Nature. Date of publication 2014 Jun 5;volume 510(7503):157-61.
1. Nature. 2014 Jun 5;510(7503):157-61. doi: 10.1038/nature13199. Epub 2014 Apr 23.
Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin
inflammation.
Riol-Blanco L(1), Ordovas-Montanes J(1), Perro M(2), Naval E(2), Thiriot A(2),
Alvarez D(2), Paust S(3), Wood JN(4), von Andrian UH(2).
Author information:
(1)1] Department of Microbiology and Immunobiology, Harvard Medical School,
Boston, Massachusetts 02115, USA [2].
(2)Department of Microbiology and Immunobiology, Harvard Medical School, Boston,
Massachusetts 02115, USA.
(3)1] Department of Microbiology and Immunobiology, Harvard Medical School,
Boston, Massachusetts 02115, USA [2] Department of Pediatrics, Baylor College of
Medicine, Houston, Texas 77030, USA.
(4)Institute for Biomedical Research, University College London, London WC1E 6BT,
UK.
Comment in
Nat Rev Immunol. 2014 Jun;14(6):354.
Cell Res. 2014 Sep;24(9):1021-2.
J Dtsch Dermatol Ges. 2014 Sep;12(9):833.
The skin has a dual function as a barrier and a sensory interface between the
body and the environment. To protect against invading pathogens, the skin
harbours specialized immune cells, including dermal dendritic cells (DDCs) and
interleukin (IL)-17-producing γδ T (γδT17) cells, the aberrant activation of
which by IL-23 can provoke psoriasis-like inflammation. The skin is also
innervated by a meshwork of peripheral nerves consisting of relatively sparse
autonomic and abundant sensory fibres. Interactions between the autonomic nervous
system and immune cells in lymphoid organs are known to contribute to systemic
immunity, but how peripheral nerves regulate cutaneous immune responses remains
unclear. We exposed the skin of mice to imiquimod, which induces IL-23-dependent
psoriasis-like inflammation. Here we show that a subset of sensory neurons
expressing the ion channels TRPV1 and Nav1.8 is essential to drive this
inflammatory response. Imaging of intact skin revealed that a large fraction of
DDCs, the principal source of IL-23, is in close contact with these nociceptors.
Upon selective pharmacological or genetic ablation of nociceptors, DDCs failed to
produce IL-23 in imiquimod-exposed skin. Consequently, the local production of
IL-23-dependent inflammatory cytokines by dermal γδT17 cells and the subsequent
recruitment of inflammatory cells to the skin were markedly reduced. Intradermal
injection of IL-23 bypassed the requirement for nociceptor communication with
DDCs and restored the inflammatory response. These findings indicate that
TRPV1(+)Nav1.8(+) nociceptors, by interacting with DDCs, regulate the IL-23/IL-17
pathway and control cutaneous immune responses.
DOI: 10.1038/nature13199
PMCID: PMC4127885
PMID: 24759321 [Indexed for MEDLINE]
