{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:01:13Z","timestamp":1772517673621,"version":"3.50.1"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Chronic type 2 inflammation is known to drive the neuroplasticity of both afferent and efferent vagal nerves innervating many organs. This results in increased neuronal density and sensitivity, possibly contributing to pathologies such as eczema and asthma. However, the mechanisms driving these neuronal changes, particularly in sensory pathways, remain poorly understood, and appropriate\n                    <jats:italic>in vitro<\/jats:italic>\n                    models for their study are lacking. Here, we describe the differentiation of sensory neurons from human pluripotent stem cells. The generation of sensory neurons was validated by verifying the expression of sensory neuron markers, such as \u03b23-tubulin, PGP9.5, TRPV1, Nav1.8, and Piezo1\/2, using immunofluorescence, flow cytometry, and RNA sequencing, as well as functional responsiveness to capsaicin using calcium imaging and spontaneous firing using a multi-electrode array. We exposed these hPSC-derived sensory neurons to TGF-\u03b2 or type 2 cytokines IL-4 and IL-13, both of which play important roles in asthmatic airway remodeling. Both treatments induced neuroplasticity-related changes, such as increased network density and neuronal sensitivity in sensory neurons, albeit more strongly with TGF-\u03b2 than with IL-4 + IL-13. Our results show robust and reproducible generation of functional hPSC-derived sensory neurons and their usability as a model to investigate the mechanisms underlying neuroplasticity. Furthermore, our findings support a role of TGF-\u03b2 and type 2 cytokines in the development of neuroplasticity.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1705880","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T05:23:45Z","timestamp":1772515425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TGF-\u03b2 and IL-4 + IL-13 induce neuroplasticity in an in vitro model of hPSC-derived sensory neurons"],"prefix":"10.3389","volume":"17","author":[{"given":"Carli S.","family":"Koster","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen","place":["Groningen, Netherlands"]},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen (UMCG), University of Groningen","place":["Groningen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. Sophie T.","family":"Bos","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen","place":["Groningen, Netherlands"]},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen (UMCG), University of Groningen","place":["Groningen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Lavitola","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen","place":["Groningen, Netherlands"]},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen (UMCG), University of Groningen","place":["Groningen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaly","family":"Balogh","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen","place":["Groningen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbro N.","family":"Melgert","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen","place":["Groningen, Netherlands"]},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen (UMCG), University of Groningen","place":["Groningen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinoud","family":"Gosens","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen","place":["Groningen, Netherlands"]},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen (UMCG), University of 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