Your browser doesn't support javascript.
loading
Nonpeptidergic neurons suppress mast cells via glutamate to maintain skin homeostasis.
Zhang, Shiqun; Edwards, Tara N; Chaudhri, Virendra K; Wu, Jianing; Cohen, Jonathan A; Hirai, Toshiro; Rittenhouse, Natalie; Schmitz, Elizabeth G; Zhou, Paul Yifan; McNeil, Benjamin D; Yang, Yi; Koerber, H Richard; Sumpter, Tina L; Poholek, Amanda C; Davis, Brian M; Albers, Kathryn M; Singh, Harinder; Kaplan, Daniel H.
Afiliación
  • Zhang S; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Edwards TN; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Chaudhri VK; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Center for Systems Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Wu J; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; School of Medicine, Tsinghua University, No. 1 Tsinghua Yuan, Haidian District, Beijing 100084, China.
  • Cohen JA; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Hirai T; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Rittenhouse N; Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
  • Schmitz EG; Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
  • Zhou PY; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • McNeil BD; Division of Allergy & Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
  • Yang Y; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
  • Koerber HR; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Sumpter TL; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Poholek AC; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
  • Davis BM; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Albers KM; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Singh H; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Center for Systems Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Kaplan DH; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address: dankaplan@pitt.edu.
Cell ; 184(8): 2151-2166.e16, 2021 04 15.
Article en En | MEDLINE | ID: mdl-33765440
Cutaneous mast cells mediate numerous skin inflammatory processes and have anatomical and functional associations with sensory afferent neurons. We reveal that epidermal nerve endings from a subset of sensory nonpeptidergic neurons expressing MrgprD are reduced by the absence of Langerhans cells. Loss of epidermal innervation or ablation of MrgprD-expressing neurons increased expression of a mast cell gene module, including the activating receptor, Mrgprb2, resulting in increased mast cell degranulation and cutaneous inflammation in multiple disease models. Agonism of MrgprD-expressing neurons reduced expression of module genes and suppressed mast cell responses. MrgprD-expressing neurons released glutamate which was increased by MrgprD agonism. Inhibiting glutamate release or glutamate receptor binding yielded hyperresponsive mast cells with a genomic state similar to that in mice lacking MrgprD-expressing neurons. These data demonstrate that MrgprD-expressing neurons suppress mast cell hyperresponsiveness and skin inflammation via glutamate release, thereby revealing an unexpected neuroimmune mechanism maintaining cutaneous immune homeostasis.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Ácido Glutámico / Mastocitos / Neuronas Límite: Animals Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Ácido Glutámico / Mastocitos / Neuronas Límite: Animals Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos