Mast cells, cortistatin, and its receptor, MRGPRX2, are linked to the pathogenesis of chronic prurigo

Kolkhir P., Pyatilova P., Ashry T., Jiao Q., Abad-Perez A. T., Altrichter S., ...Daha Fazla

Journal of Allergy and Clinical Immunology, cilt.149, sa.6, ss.1998, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 149 Sayı: 6
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.jaci.2022.02.021
  • Dergi Adı: Journal of Allergy and Clinical Immunology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1998
  • Anahtar Kelimeler: Chronic prurigo, cortistatin, mast cell, degranulation, MRGPRX2, severity
  • Erciyes Üniversitesi Adresli: Hayır

Özet

© 2022 American Academy of Allergy, Asthma & ImmunologyBackground: Chronic prurigo (CPG) is characterized by intensive itch and interactions among nerves, neuropeptides, and mast cells (MCs). The role of some neuropeptides such as cortistatin (CST) and its receptor, Mas-related G protein–coupled receptor X2 (MRGPRX2), in CPG remains poorly investigated. Objectives: We evaluated first whether CST activates human skin MCs, and second whether CST and MRGPRX2 are expressed in the skin of CPG patients, and by which cells. Methods: Skin prick tests and microdialysis with CST were performed in 6 and 1 healthy volunteers, respectively. Degranulation of human skin MCs was assessed using β-hexosaminidase and histamine release assays. Skin samples from 10 patients with CPG and 10 control subjects were stained for CST, MCs, and MRGPRX2 (protein and mRNA) using immunohistochemistry, immunofluorescence, and/or in situ hybridization. Flow cytometry was used to assess CST in human skin MCs. MRGPRX2 levels were measured in serum by ELISA. Results: CST induced concentration-dependent degranulation of human skin MCs in vivo and ex vivo. Skin lesions of CPG patients exhibited markedly higher numbers of CST-expressing cells, CST-expressing MCs, MRGPRX2-expressing cells, and MRGPRX2 mRNA-expressing cells than nonlesional skin. MCs were the main MRGPRX2 mRNA-expressing cells in the lesions of most CPG patients (70%). Stimulation of human skin MCs with anti-IgE led to a release of CST. The number of MRGPRX2-expressing cells correlated with disease severity (r = 0.649, P =.04). MRGPRX2 serum levels in CPG patients correlated with disease severity (r = 0.704, P =.023) and quality-of-life impairment (r = 0.687, P =.028). Conclusions: CST and MRGPRX2 may contribute to the pathogenesis of CPG and should be evaluated in further studies as potential biomarkers and novel therapeutic targets.