{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:56:53Z","timestamp":1773053813748,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Morinaga Milk Industry Co. Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lactoferrin (LF) is present in tears, nasal secretions, saliva, and milk and maintains mucosal homeostasis. The palatine tonsils represent the first immune tissue to recognize pathogens invading the oral cavity via Toll-like receptors (TLRs). We aimed to investigate the effects of bovine LF on tonsillar immune cells stimulated with ligands of TLR7 or TLR9, which recognize viral single-stranded RNA or bacterial unmethylated CpG DNA. Mononuclear cells isolated from palatine tonsils of patients with recurrent tonsillitis or immunoglobulin A (IgA) nephropathy were cultured with LF, TLR7, or TLR9 ligands. Under TLR7 stimulation, LF enhanced the activation of plasmacytoid dendritic cells (pDCs), T-killer cells, and B cells without inducing inflammatory cytokines. In contrast, under TLR9 stimulation, LF suppressed the activation of pDCs, myeloid dendritic cells, T-helper cells, T-killer cells, B cells, and natural killer cells, as well as the production of TNF-\u03b1 and IL-6. Moreover, LF decreased the production of the B-cell activation factor (BAFF), a proliferation-inducing ligand (APRIL), and galactose-deficient IgA1, all of which are risk factors of IgA nephropathy. Overall, LF may enhance the immune response against viruses and contribute to immune tolerance against commensal bacteria in the palatine tonsils, indicating potential benefits in managing cold-like symptoms, recurrent tonsillitis, and IgA nephropathy.<\/jats:p>","DOI":"10.3390\/ijms27052442","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T14:43:07Z","timestamp":1772808187000},"page":"2442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bovine Lactoferrin Modulates Mononuclear Cell Activity in Human Palatine Tonsils"],"prefix":"10.3390","volume":"27","author":[{"given":"Takumi","family":"Yago","sequence":"first","affiliation":[{"name":"R&D Division, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama 252-8583, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chisane","family":"Kujirai","sequence":"additional","affiliation":[{"name":"R&D Division, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama 252-8583, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotsugu","family":"Oda","sequence":"additional","affiliation":[{"name":"R&D Division, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama 252-8583, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2457-9063","authenticated-orcid":false,"given":"Takahiro","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2-jo, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4826-9829","authenticated-orcid":false,"given":"Hisataka","family":"Ominato","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2-jo, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risa","family":"Wakisaka","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2-jo, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5899-3410","authenticated-orcid":false,"given":"Ryosuke","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2-jo, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8506-928X","authenticated-orcid":false,"given":"Michihisa","family":"Kono","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2-jo, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidekiyo","family":"Yamaki","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2-jo, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6957-6206","authenticated-orcid":false,"given":"Kenzo","family":"Ohara","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2-jo, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-671X","authenticated-orcid":false,"given":"Takumi","family":"Kumai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2-jo, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7670-7366","authenticated-orcid":false,"given":"Miyuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"R&D Division, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama 252-8583, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miki","family":"Takahara","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2-jo, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s12016-025-09071-0","article-title":"Novel Findings on the Development and Immunological Functions of Palatine Tonsils","volume":"68","author":"Abulikemu","year":"2025","journal-title":"Clin. 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