Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch<\/a><\/p>\nLandon K. Oetjen,1,2 Madison R. Mack,1,2 Jing Feng,1,3 Timothy M. Whelan,1,2 Haixia Niu,1,2 Changxiong J. Guo,1,3
\nSisi Chen,4 Anna M. Trier,1,2 Amy Z. Xu,1,2 Shivani V. Tripathi,1,2 Jialie Luo,1,3 Xiaofei Gao,1,3 Lihua Yang,5
\nSamantha L. Hamilton,5 Peter L. Wang,6 Jonathan R. Brestoff,6 M. Laurin Council,2 Richard Brasington,7
\nAndra \u0301 s Schaffer,2,6 Frank Brombacher,8 Chyi-Song Hsieh,6,7 Robert W. Gereau IV,3 Mark J. Miller,5 Zhou-Feng Chen,1,3 Hongzhen Hu,1,3 Steve Davidson,4 Qin Liu,1,3 and Brian S. Kim1,2,3,6,9,*
\n1Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, USA
\n2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
\n3Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA
\n4Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
\n5Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA 6Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
\n7Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA 8International Centre for Genetic Engineering and Biotechnology and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, University of Cape Town, Cape Town 7700, South Africa
\n9Lead Contact
\n*Correspondence: briankim@wustl.edu
\nhttp:\/\/dx.doi.org\/10.1016\/j.cell.2017.08.006<\/p>\n
Mammals have evolved neurophysiologic reflexes, such as coughing and scratching, to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also asso- ciated with chronic inflammatory diseases, including asthma and atopic dermatitis. However, the mecha- nisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Ra and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies mark- edly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, this study reveals an evolutionarily conserved para- digm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior.<\/p>\n","protected":false},"excerpt":{"rendered":"
Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch Landon K. Oetjen,1,2 Madison R. Mack,1,2 Jing Feng,1,3 Timothy M. Whelan,1,2 Haixia Niu,1,2 Changxiong J. Guo,1,3 Sisi Chen,4 Anna M. Trier,1,2 Amy Z. Xu,1,2 Shivani V. Tripathi,1,2 Jialie Luo,1,3 Xiaofei Gao,1,3 Lihua Yang,5 […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1539"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1539"}],"version-history":[{"count":1,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1539\/revisions"}],"predecessor-version":[{"id":1541,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1539\/revisions\/1541"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1539"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1539"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1539"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}