{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T06:54:48Z","timestamp":1768892088349,"version":"3.49.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:00:00Z","timestamp":1619740800000},"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:p>The intestinal mucosa is lined by epithelial cells, which are key cells to sustain gut homeostasis. Food allergy is an immune-mediated adverse reaction to food, likely due to defective regulatory circuits. <jats:italic>Tsukamurella inchonensis<\/jats:italic> is a non-pathogenic bacterium with immunomodulatory properties. We hypothesize that the anti-inflammatory effect of dead <jats:italic>T<\/jats:italic>.\u00a0<jats:italic>inchonensis<\/jats:italic> on activated epithelial cells modulates milk allergy through the restoration of tolerance in a mouse model. Epithelial cells (Caco-2 and enterocytes from mouse gut) and macrophages were stimulated with <jats:italic>T<\/jats:italic>. <jats:italic>inchonensis<\/jats:italic> and induction of luciferase under the NF-\u03baB promoter, ROS and cytokines production were studied. Balb\/c mice were mucosally sensitized with cow\u00b4s milk proteins plus cholera toxin and orally challenged with the allergen to evidence hypersensitivity symptoms. After that, mice were orally administered with heat-killed <jats:italic>T<\/jats:italic>. <jats:italic>inchonensis<\/jats:italic> as treatment and then challenged with the allergen. The therapeutic efficacy was <jats:italic>in vivo<\/jats:italic> (clinical score and cutaneous test) and <jats:italic>in vitro<\/jats:italic> (serum specific antibodies and cytokines-ELISA, and cell analysis-flow cytometry) evaluated. Heat-killed <jats:italic>T<\/jats:italic>. <jats:italic>inchonensis<\/jats:italic> modulated the induction of pro-inflammatory chemokines, with an increase in anti-inflammatory cytokines by intestinal epithelial cells and by macrophages with decreased OX40L expression. <jats:italic>In vivo<\/jats:italic>, oral administration of <jats:italic>T<\/jats:italic>. <jats:italic>inchonensis<\/jats:italic> increased the frequency of lamina propria CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> T cells, and clinical signs were lower in <jats:italic>T<\/jats:italic>. <jats:italic>inchonensis<\/jats:italic>-treated mice compared with milk-sensitized animals. <jats:italic>In vivo<\/jats:italic> depletion of Tregs (anti-CD25) abrogated <jats:italic>T<\/jats:italic>. <jats:italic>inchonensis<\/jats:italic> immunomodulation. In conclusion, these bacteria suppressed the intestinal inflammatory immune response to reverse food allergy.<\/jats:p>","DOI":"10.3389\/fimmu.2021.641597","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T07:49:00Z","timestamp":1619768940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mucosal Immunoregulatory Properties of Tsukamurella inchonensis to Reverse Experimental Food Allergy"],"prefix":"10.3389","volume":"12","author":[{"given":"Paola L.","family":"Smaldini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando M.","family":"Trejo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gast\u00f3n P.","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego 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