Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation
Lorena Riol-Blanco,Jose Ordovas-Montanes,Mario Perro,Elena Naval,Aude Thiriot,David Alvarez,Silke Paust,John N. Wood,Ulrich H. von Andrian +8 more
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TLDR
Findings indicate that TRPV1+Nav1.8+ nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway and control cutaneous immune responses.Abstract:
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.read more
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Journal ArticleDOI
Interleukin-22: Immunobiology and Pathology
TL;DR: The current understanding of IL-22 is assessed, including its physiologic and pathologic effects on epithelial cell function, which are linked to several conditions involving inflammatory tissue pathology.
Journal ArticleDOI
Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch
Landon K. Oetjen,Madison R. Mack,Jing Feng,Timothy M. Whelan,Haixia Niu,Changxiong J. Guo,Sisi Chen,Anna M. Trier,Amy Z. Xu,Shivani V. Tripathi,Jialie Luo,Xiaofei Gao,Lihua Yang,Samantha L. Hamilton,Peter L. Wang,Jonathan R. Brestoff,Richard Brasington,Andras Schaffer,Frank Brombacher,Chyi-Song Hsieh,Robert W. Gereau,Mark J. Miller,Zhou-Feng Chen,Hongzhen Hu,Steve Davidson,Qin Liu,Brian S. Kim +26 more
TL;DR: An evolutionarily conserved paradigm is revealed in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior, including chronic itch.
Journal ArticleDOI
Nociceptor Sensory Neuron-Immune Interactions in Pain and Inflammation.
TL;DR: The dialog between nociceptor neurons and the immune system is a fundamental aspect of inflammation, both acute and chronic, and a better understanding of these interactions could produce approaches to treat chronic pain and inflammatory diseases.
Journal ArticleDOI
K+ Efflux-Independent NLRP3 Inflammasome Activation by Small Molecules Targeting Mitochondria
Christina J. Groß,Ritu Mishra,Katharina S. Schneider,Guillaume Médard,Jennifer Wettmarshausen,Daniela Dittlein,Hexin Shi,Oliver Gorka,Paul-Albert Koenig,Stephan Fromm,Giovanni Magnani,Tamara Cikovic,Lara Hartjes,Joachim Smollich,Avril A. B. Robertson,Mark E. Cooper,Marc Schmidt-Supprian,Michael Schuster,Kate Schroder,Petr Broz,Claudia Traidl-Hoffmann,Bruce Beutler,Bernhard Kuster,Jürgen Ruland,Sabine Schneider,Fabiana Perocchi,Olaf Groß +26 more
TL;DR: The mechanism of inflammasome activation by imiquimod and the related molecule CL097 was investigated and it was determined that K+ efflux was dispensable for NLRP3 activation by these compounds.
Journal ArticleDOI
The immunological anatomy of the skin
TL;DR: An overview of the key findings and concepts of cutaneous immunity in association with skin anatomy are provided and how cutaneous immune cells fine-tune physiological responses in the skin are discussed.
References
More filters
Journal ArticleDOI
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
Mehrdad Matloubian,Charles G. Lo,Guy Cinamon,Matthew J. Lesneski,Ying Xu,Volker Brinkmann,Maria L. Allende,Richard L. Proia,Jason G. Cyster +8 more
TL;DR: It is established that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.
Journal ArticleDOI
Identification of splenic reservoir monocytes and their deployment to inflammatory sites
Filip K. Swirski,Matthias Nahrendorf,Martin Etzrodt,Martin Etzrodt,Moritz Wildgruber,Virna Cortez-Retamozo,Peter Panizzi,Jose-Luiz Figueiredo,Rainer H. Kohler,Aleksey Chudnovskiy,Peter Waterman,Elena Aikawa,Thorsten R. Mempel,Peter Libby,Ralph Weissleder,Mikael J. Pittet +15 more
TL;DR: It is shown that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation and identifies splenic monocytes as a resource that the body exploits to regulate inflammation.
Journal ArticleDOI
Interleukin-22, a T H 17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
Yan Zheng,Dimitry M. Danilenko,Patricia Valdez,Ian Kasman,Jeffrey Eastham-Anderson,Jianfeng Wu,Wenjun Ouyang +6 more
TL;DR: The results suggest that TH17 cells, through the production of both IL-22 and IL-17, might have essential functions in host defence and in the pathogenesis of autoimmune diseases such as psoriasis.
Journal ArticleDOI
In Vivo Depletion of CD11c+ Dendritic Cells Abrogates Priming of CD8+ T Cells by Exogenous Cell-Associated Antigens
Steffen Jung,Derya Unutmaz,Phillip Wong,Gen Ichiro Sano,Kenia De Los Santos,Tim Sparwasser,Shengji Wu,Sri Vuthoori,Kyung Ko,Fidel Zavala,Eric G. Pamer,Dan R. Littman,Richard A. Lang +12 more
TL;DR: A novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo is reported and it is shown that in vivo DC are required to cross-prime CTL precursors.
Journal ArticleDOI
Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis
Leslie van der Fits,Sabine Mourits,Jane S. A. Voerman,Marius Kant,Louis Boon,Jon D. Laman,Ferry Cornelissen,Anne-Marie Mus,Edwin Florencia,Errol P. Prens,Erik Lubberts +10 more
TL;DR: The sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis.
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