{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:24:59Z","timestamp":1789075499878,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dry eye disease (DED) is an inflammatory disorder in which CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells play a significant role in its pathogenesis. A CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell subset termed granulocyte\u2010macrophage colony\u2010stimulating factor\u2010producing T helper (ThGM) cells would contribute to DED pathogenesis. However, the mechanisms by which the activity of ThGM cells is modulated are not thoroughly understood. In this research, we characterized the effects of neurokinin 1 receptor (NK1R) and neurokinin 2 receptor (NK2R) on ThGM cells and T helper 1 (Th1) cells in a murine DED model. We found that ThGM cells expressed NK1R and NK2R, whereas Th1 cells predominantly expressed NK1R. Furthermore, substance P and neurokinin A (NKA), the ligands of NK1R and NK2R, were upregulated in post\u2010DED LNs and conjunctivae. Substance P significantly promoted granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF) expression while mildly upregulating the expression of interferon\u2010gamma (IFN\u2010\u03b3) and interleukin 2 (IL\u20102) in ThGM cells. By contrast, NKA did not change GM\u2010CSF expression but significantly increased IFN\u2010\u03b3 expression in ThGM cells. Importantly, the adoptive transfer of NK1R\u2010expressing ThGM cells significantly exacerbated DED, whereas the transfer of NK1R\u2010knockdown ThGM cells weakly aggravated DED. NK2R knockdown in ThGM cells did not affect DED progression. In conclusion, this study identifies the substance P\u2010NK1R axis as a novel mechanism that reinforces the pathogenicity of ThGM cells in DED.\n                  <\/jats:p>","DOI":"10.1111\/sji.13434","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:44:40Z","timestamp":1736469880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Substance P and neurokinin 1 receptor boost the pathogenicity of granulocyte\u2010macrophage colony\u2010stimulating factor\u2010producing T helper cells in dry eye disease"],"prefix":"10.1111","volume":"101","author":[{"given":"Hua","family":"Rong","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Shanghai Jiangong Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shanghai East Hospital 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