{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:11:45Z","timestamp":1789805505141,"version":"4.0.1"},"reference-count":67,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF1200803"],"award-info":[{"award-number":["2021YFF1200803"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF1200404"],"award-info":[{"award-number":["2021YFF1200404"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1201200"],"award-info":[{"award-number":["2021YFA1201200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1967217"],"award-info":[{"award-number":["U1967217"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The olfactory mucosa serves as both a sensory organ and an immune barrier to protect against bacterial and viral invasion and other insults. It is unclear how different types of olfactory mucosal cells coordinate and contribute to these two functions. We set out to reveal the critical roles of a subset of microvillous cells of the mucosa, olfactory tuft cells, in protecting and reconstructing this vital olfactory sensory organ. We first validated the expression of canonical gustatory signalling proteins and other molecular markers in olfactory tuft cells. Genetic disruption of the\n                    <jats:italic>Gng13<\/jats:italic>\n                    and\n                    <jats:italic>Trpm5<\/jats:italic>\n                    genes that encode the two gustatory signalling proteins, G protein subunit G\u03b313 and transient receptor potential ion channel Trpm5, respectively, resulted in elevated basal inflammation and enhanced activation of the quiescent stem cells\u2014horizontal basal cells (HBCs) in the mucosa. Nasal infection of H1N1 influenza virus further exacerbated the inflammation and delayed the resolution of inflammation in the mutant mucosa, including more immune cell infiltration, augmented cytokine production and cell death, increased HBC proliferation and direct differentiation into tuft cells, and prolonged olfactory tuft cell hyperplasia. Cytokine treatment of the cultured olfactory epithelial organoids indicated that the cytokines that were found to be elevated in the mutant mucosa, including interleukin\u20104 (IL\u20104), IL\u201013 and interferon\u2010\u03b3 (INF\u2010\u03b3), are able to stimulate HBC activation. Together, our results indicate that olfactory tuft cells play an important role in maintaining the baseline inflammation under the steady\u2010state condition, and altering inflammatory magnitude and modulating HBC activation and differentiation in the olfactory mucosa following the viral infection. Our findings shed light on new roles of olfactory tuft cells in innate immune response, quiescent stem cell activation and neuroimmune interactions, and provide novel therapeutic targets for preventing and treating stem cell\u2010related olfactory disorders such as chronic rhinosinusitis and long COVID.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70281","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:31:36Z","timestamp":1789803096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Olfactory Tuft Cells Are Critical to Basal Inflammation, Innate Immune Response to Viral Infection, and Modulation of Quiescent Stem Cell Activation, Proliferation and Differentiation"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8851-9871","authenticated-orcid":false,"given":"Sai\u2010Sai","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Life Sciences, Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Sen","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Hong","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Defu","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1715-6805","authenticated-orcid":false,"given":"Yushi","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8624-5591","authenticated-orcid":false,"given":"Ruhong","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Zhejiang University  Hangzhou Zhejiang China"},{"name":"Institute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3400-0685","authenticated-orcid":false,"given":"Liquan","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"issue":"6","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41577-023-00972-9","article-title":"Olfactory Immunology: The Missing Piece in Airway and CNS Defence","volume":"24","author":"Wellford S. 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