{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:05:13Z","timestamp":1789013113149,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nippi Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Collagen peptides have been widely used as a food supplement. After ingestion of collagen peptides, oligopeptides containing hydroxyproline (Hyp), which are known to have some physiological activities, are detected in peripheral blood. However, the effects of collagen\u2010peptide administration on immune response are unclear. In the present study, we tested the effects of collagen\u2010peptide ingestion on allergic response and the effects of collagen\u2010derived oligopeptides on CD4<jats:sup>+<\/jats:sup> T\u2010cell differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BALB\/c mice fed a collagen\u2010peptide diet were immunized with ovalbumin (OVA), and their serum IgE and IgG levels, active cutaneous anaphylaxis, and cytokine secretion by splenocytes were examined. Naive CD4<jats:sup>+<\/jats:sup> T cells were stimulated with anti\u2010CD3 and anti\u2010CD28 in the presence of collagen\u2010derived oligopeptides, and the expression of IFN\u2010\u03b3, IL\u20104, and Foxp3 was analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In an active anaphylaxis model, oral administration of collagen peptides suppressed serum OVA\u2010specific immunoglobulin E (IgE) production and diminished anaphylaxis responses. In this model, the ingestion of collagen peptides skewed the pattern of cytokine production by splenocytes toward T\u2010helper (Th) type 1 and regulatory T (Treg) cells. In vitro T\u2010helper cell differentiation assays showed that Hyp\u2010containing oligopeptides promoted Th1 differentiation by upregulating IFN\u2010\u03b3\u2010induced signal transducer and activator of transcription 1 (STAT1) signaling. These oligopeptides also promoted the development of Foxp3<jats:sup>+<\/jats:sup> Treg cells in response to antigen stimulation in the presence of TGF\u2010\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Collagen\u2010peptide ingestion suppresses allergic responses by skewing the balance of CD4<jats:sup>+<\/jats:sup> T cells toward Th1 and Treg cells and seems to be a promising agent for preventing allergies and inflammatory diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.213","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T05:22:41Z","timestamp":1517462561000},"page":"245-255","source":"Crossref","is-referenced-by-count":35,"title":["Collagen\u2010derived peptides modulate CD4<sup>+<\/sup> T\u2010cell differentiation and suppress allergic responses in mice"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9497-7557","authenticated-orcid":false,"given":"Akihiko","family":"Nishikimi","sequence":"first","affiliation":[{"name":"Department of Biosciences School of Science Kitasato University Sagamihara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoh\u2010ichi","family":"Koyama","sequence":"additional","affiliation":[{"name":"Research Institute of Biomatrix Nippi Inc. 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