{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:51:56Z","timestamp":1789051916564,"version":"build-2803163510"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>In addition to serving as the primary effector cells against infections, neutrophils have been implicated in the regulation of both innate and adaptive immunity. In this study, we aimed to investigate the role of neutrophils in the regulation of the immune system under physiological conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:italic>in vivo<\/jats:italic> effect of neutrophils on the immune system was examined using neutropenic mice. The interaction between neutrophils and \u03b3\u03b4 T cells was investigated using an <jats:italic>in vitro<\/jats:italic> co-culture system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>Unexpectedly, we observed an accumulation of \u03b3\u03b4 T cells in the cervical lymph nodes of neutropenic mice. Transcriptomic analysis revealed that these \u03b3\u03b4 T cells exhibited unique expression profiles of cell surface molecules and genes involved in defense responses. Further characterization indicated that the accumulated \u03b3\u03b4 T cells were IL-17 producing CD44<jats:sup>+<\/jats:sup>CD62L<jats:sup>\u2212<\/jats:sup>CD27<jats:sup>\u2212<\/jats:sup> memory cells. Additionally, <jats:italic>in vitro<\/jats:italic> experiments demonstrated that neutrophils could inhibit the function of IL-17A producing \u03b3\u03b4 T cells by inducing cell death in a contact-dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This present study demonstrates that neutrophils negatively regulate IL-17 producing \u03b3\u03b4 T cells under physiological conditions. Given that IL-17A is a critical cytokine for the recruitment of neutrophils to peripheral tissues, our study suggests that the crosstalk between neutrophils and IL-17A producing \u03b3\u03b4 T cells is a crucial mechanism for maintaining immune homeostasis under physiological conditions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1542191","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T08:51:28Z","timestamp":1742460688000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Neutrophils negatively control IL-17A-producing \u03b3\u03b4 T cell frequencies in a contact-dependent manner under physiological 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