{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T23:23:56Z","timestamp":1782516236837,"version":"3.54.5"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, Taiwan, ROC","award":["MOST-107-2314-B-303-017"],"award-info":[{"award-number":["MOST-107-2314-B-303-017"]}]},{"name":"Ministry of Science and Technology, Taiwan, ROC","award":["DTCRD107(2)-E-01-02"],"award-info":[{"award-number":["DTCRD107(2)-E-01-02"]}]},{"name":"Ministry of Science and Technology, Taiwan, ROC","award":["TCMF-SP108-02(108)"],"award-info":[{"award-number":["TCMF-SP108-02(108)"]}]},{"name":"Buddhist DaLin Tzu-Chi Hospital, Taiwan, ROC","award":["MOST-107-2314-B-303-017"],"award-info":[{"award-number":["MOST-107-2314-B-303-017"]}]},{"name":"Buddhist DaLin Tzu-Chi Hospital, Taiwan, ROC","award":["DTCRD107(2)-E-01-02"],"award-info":[{"award-number":["DTCRD107(2)-E-01-02"]}]},{"name":"Buddhist DaLin Tzu-Chi Hospital, Taiwan, ROC","award":["TCMF-SP108-02(108)"],"award-info":[{"award-number":["TCMF-SP108-02(108)"]}]},{"DOI":"10.13039\/501100005925","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["MOST-107-2314-B-303-017"],"award-info":[{"award-number":["MOST-107-2314-B-303-017"]}],"id":[{"id":"10.13039\/501100005925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005925","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["DTCRD107(2)-E-01-02"],"award-info":[{"award-number":["DTCRD107(2)-E-01-02"]}],"id":[{"id":"10.13039\/501100005925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005925","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["TCMF-SP108-02(108)"],"award-info":[{"award-number":["TCMF-SP108-02(108)"]}],"id":[{"id":"10.13039\/501100005925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory disease and is highly linked with the expression of the human leukocytic antigen-B*27 (HLA-B*27) genotype. HLA-B*27 heavy chain (B*27-HC) has an innate characteristic to slowly fold, resulting in the accumulation of the misfolded B*27-HC and the formation of homo-oligomeric B*27-HC molecules. The homo-oligomeric B*27-HC can act as a ligand of KIR3DL2. Interaction of the homo-oligomeric B*27-HC molecules with KIR3DL2 will trigger the survival and activation of KIR3DL2-positive NK cells. However, the effects of homo-oligomeric B*27-HC molecules associated with KIR3DL2 on the cytotoxic activity of NK cells and their cytokine expressions remain unknown. Materials and Methods: HLA-B*-2704-HC was overexpressed in the HMy2.C1R (C1R) cell line. Western blotting and quantitative RT-PCR were used to analyze the protein expression and cytokine expression, respectively, when C1R-B*-2704 cells that overexpress B*2704-HC were co-cultured with NK-92MI cells. Flow cytometry was used to analyze the cytotoxicity mediated by NK-92MI cells. Results: Our results revealed that NK-92MI cells up-regulated the expression of perforin and enhanced the cytotoxic activity via augmentation of PI3K\/AKT signaling after co-culturing with C1R-B*2704 cells. Suppression of the dimerized B*27-HC formation or treatment with an inhibitor of PI3K, LY294002, or with an anti-B*27-HC monoclonal antibody can reduce the perforin expression of NK-92MI after co-culturing with C1R-B*-2704. Co-culturing with C1R-B*-2704 cells suppressed the TNF-\u03b1 and IL6 expressions of NK-92MI cells. Conclusion: Stimulation of NK cell-mediated cytotoxicity by homo-oligomeric B*27-HC molecules may contribute to the pathogenesis of AS.<\/jats:p>","DOI":"10.3390\/medicina58101411","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T04:00:02Z","timestamp":1665288002000},"page":"1411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["HLA-B*27 Heavy Chain Homo-Oligomers Promote the Cytotoxicity of NK Cells via Activation of PI3K\/AKT Signaling"],"prefix":"10.3390","volume":"58","author":[{"given":"Hui-Chun","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Yung","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-0351","authenticated-orcid":false,"given":"Ming-Chi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsien-Yu","family":"Huang Tseng","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Qin","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning-Sheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsien-Bin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, National Chung Cheng University, Chiayi 621, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.0105-2896.2009.00865.x","article-title":"From HLA-B27 to spondyloarthritis: A journey through the ER","volume":"233","author":"Colbert","year":"2010","journal-title":"Immunol. 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