Fernández-Tomé, SamuelIndiano-Romacho, PedroMora-Gutiérrez, IrenePérez-Rodríguez, LeticiaOrtega Moreno, LorenaMarin, Alicia CBaldán-Martín, MontseMoreno-Monteagudo, Jose AndrésSantander, CecilioChaparro, MaríaHernández-Ledesma, BlancaGisbert P., JavierBernardo, David2024-06-202024-06-202021-04-22S. Fernández-Tomé, P. Indiano-Romacho, I. Mora-Gutiérrez, L. Pérez-Rodríguez, L. OrtegaMoreno, A. C. Marin, M. Baldán-Martín, J. A. Moreno-Monteagudo, C. Santander, M. Chaparro, B. Hernández-Ledesma, J. P. Gisbert, D. Bernardo, Lunasin Peptide is a Modulator of the Immune Response in the Human Gastrointestinal Tract. Mol. Nutr. Food Res. 2021, 65, 2001034. https://doi.org/10.1002/mnfr.2020010341613-4125 (print)1613-4133 (online)https://hdl.handle.net/10115/34376Introduction: Lunasin is a soybean bioactive peptide with a variety of beneficial properties against chronic disorders. However, its effect in human primary intestinal cells remains unknown. Hence, this study aims to characterize its ex vivo biological activity in the human intestinal mucosa. Methods and Results: Human intestinal biopsies, obtained from healthy controls, are ex vivo conditioned with lunasin both in the presence/absence of lipopolysaccharide (LPS). Peptide maintains its stability during biopsy culture by HPLC-MS/MS analysis. Lunasin is bioactive in the human mucosa, as it induces IL-1𝜷, TNF-𝜶, IL-17A, CCL2, and PGE2/COX-2 gene expression together with an increased expression of tolerogenic IL-10 and TGF𝜷, while it also downregulates the expression of iNOS and subunit p65 from NF-𝜿B. Indeed, lunasin also abrogates the LPS-induced pro-inflammatory response, downregulating IL-17A, IFN𝜸, and IL-8 expression, and inducing IL-10 and TGF𝜷 expression. These results are also mirrored in the cell-free culture supernatants at the protein level by Multiplex. Moreover, lunasin further induces a regulatory phenotype and function on human intestinal conventional dendritic cell and macrophage subsets as assessed by flow cytometry. Conclusions: We hereby have characterized lunasin as an immunomodulatory peptide with potential capacity to prevent immune and inflammatory-mediated disorders in the human gastrointestinal tract.enginfo:eu-repo/semantics/article10.1002/mnfr.202001034info:eu-repo/semantics/openAccess