{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:44:28Z","timestamp":1792395868694,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Chronic cough, a distressing symptom of allergic asthma, possibly arises from the abnormal activation of airway\u2010projecting sensory neurons. Levels of interleukin (IL)\u201031, a Th2 cytokine known for its neuronal effects in pruritus, are elevated in allergic disorders; however, its role in asthma\u2010related cough remains unclear. Therefore, in this study, we aimed to determine the mechanism by which IL\u201031 influences cough\u2010associated neuronal sensitization using a\n                      <jats:italic>Dermatophagoides farinae<\/jats:italic>\n                      (\n                      <jats:italic>Derf<\/jats:italic>\n                      )\u2010induced asthma model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Wild\u2010type (WT) and\n                      <jats:italic>Il31<\/jats:italic>\n                      knockout (KO) C57BL\/6N mice were intranasally administered the\n                      <jats:italic>Derf<\/jats:italic>\n                      extract repeatedly. Lung tissues, bronchoalveolar lavage fluid, and hilar lymph nodes were analyzed via histology, flow cytometry, enzyme\u2010linked immunosorbent assay, and quantitative polymerase chain reaction. Vagal and dorsal root ganglia were assessed via immunofluorescence assay and Ca\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                      imaging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Protease\u2010activated receptor (PAR)\u20102 activity was evaluated using the agonist SLIGRL\u2010NH\n                      <jats:sub>2<\/jats:sub>\n                      .\n                      <jats:italic>Derf<\/jats:italic>\n                      upregulated\n                      <jats:italic>Il31<\/jats:italic>\n                      levels in airway tissues. Notably, immune and histological parameters were comparable between WT and\n                      <jats:italic>Il31<\/jats:italic>\n                      KO mice, indicating that IL\u201031 deficiency did not alter Th2\u2010driven inflammation. In contrast,\n                      <jats:italic>Derf<\/jats:italic>\n                      \u2010challenged WT mice exhibited increased\n                      <jats:italic>Il31ra<\/jats:italic>\n                      and\n                      <jats:italic>F2rl1<\/jats:italic>\n                      (PAR\u20102) levels and PAR\u20102\u2010positive neuron proportions in vagal ganglia, changes that were not observed in\n                      <jats:italic>Il31<\/jats:italic>\n                      KO mice. Ca\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                      imaging confirmed that PAR\u20102 responsiveness to SLIGRL\u2010NH\n                      <jats:sub>2<\/jats:sub>\n                      was enhanced only in WT asthma model mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, IL\u201031 modulated the neuronal, rather than immune, components of allergic asthma by enhancing the PAR\u20102\u2010dependent excitability of vagal sensory neurons. These findings highlight the IL\u201031\u2013PAR\u20102\u2013vagal pathway as the potential mechanism of and therapeutic target for allergen\u2010driven cough.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71731","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:46:01Z","timestamp":1788543961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Roles of Interleukin\u201031 in Allergen\u2010Driven Cough: Linking Protease\u2010Activated Receptor\u20102 Activation and Vagal Ganglion Sensitization in a\n                    <i>Dermatophagoides farinae<\/i>\n                    \u2010Induced Asthma Model"],"prefix":"10.1002","volume":"16","author":[{"given":"Takayoshi","family":"Miyamoto","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine Azabu University  Sagamihara\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiharu","family":"Ohira","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine Azabu University  Sagamihara\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Kaneki","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine Azabu University  Sagamihara\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Komuro","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine Azabu University  Sagamihara\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mana","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine Azabu University  Sagamihara\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibuki","family":"Yasuda","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine Azabu University  Sagamihara\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiichi","family":"Takagi","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine Azabu University  Sagamihara\u2010shi Kanagawa Japan"},{"name":"Japan SLC, Inc.  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