{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:56:04Z","timestamp":1790916964927,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Early-life exposure to allergens is a critical window that shapes immune development. Epidemiological and experimental evidence suggests that neonatal cytokine responses, particularly interleukin (IL)-4 and IL-5, drive type 2 immunity and increase the risk of allergic sensitization and asthma in adulthood. However, whether blocking these pathways in neonates can alter long-term susceptibility remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Neonatal BALB\/c mice were exposed to 1% aerosolized ovalbumin (OVA) for 20\u00a0min, whereas controls received PBS. A subset of OVA-exposed neonates received 0.5 mg anti-IL-4 antibody at day 0. At adulthood (8 weeks), all groups were reexposed to aerosolized OVA. Blood and lung samples were collected for analysis of eosinophils, OVA-specific IgE, and cytokine production.\n                      <jats:italic>In vitro<\/jats:italic>\n                      restimulation of lung cells was performed for type 2 cytokines (specifically IL4, IL5, and IL13) and IFN-\u03b3 profiling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mice exposed to aerosolized OVA as neonates exhibited elevated IL-4, IL-5, and IL-13, with increased eosinophilia and OVA-specific IgE, consistent with a type 2-biased response. PBS control neonatal mice challenged only in adulthood with aerosolized OVA showed no such sensitization. Strikingly, anti-IL-4 treatment at 2 days old prevented the dysregulated allergic sensitization and restored a balanced immune response, even upon OVA reexposure in adulthood. Anti-IL-4-treated neonates remained capable of mounting normal Th2 responses comparable with those observed in non-sensitized adult mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Neonatal IL-4 and IL-5 signaling critically shapes long-term eosinophilic allergic sensitization. Early blockade of IL-4 prevents lifelong allergen-specific dysregulation, highlighting potential therapeutic benefits of cytokine-targeted interventions in infancy for the prevention of allergic diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1858193","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:41:30Z","timestamp":1790916090000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal IL-4 and IL-5 signaling drives long-term inflammation after early-life allergen exposure in a mouse model of allergic sensitization"],"prefix":"10.3389","volume":"17","author":[{"given":"Brian W. 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