{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T11:07:43Z","timestamp":1788001663687,"version":"build-2784847793"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["No. 2021YFE0200300"],"award-info":[{"award-number":["No. 2021YFE0200300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["No. 2020YFA0708004"],"award-info":[{"award-number":["No. 2020YFA0708004"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["No.YJSKC-20211015"],"award-info":[{"award-number":["No.YJSKC-20211015"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["SFB 1027 A2"],"award-info":[{"award-number":["SFB 1027 A2"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["No. 82204878"],"award-info":[{"award-number":["No. 82204878"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tianjin University of Traditional Chinese Medicine","award":["No. 2021YFE0200300"],"award-info":[{"award-number":["No. 2021YFE0200300"]}]},{"name":"Tianjin University of Traditional Chinese Medicine","award":["No. 2020YFA0708004"],"award-info":[{"award-number":["No. 2020YFA0708004"]}]},{"name":"Tianjin University of Traditional Chinese Medicine","award":["No.YJSKC-20211015"],"award-info":[{"award-number":["No.YJSKC-20211015"]}]},{"name":"Tianjin University of Traditional Chinese Medicine","award":["SFB 1027 A2"],"award-info":[{"award-number":["SFB 1027 A2"]}]},{"name":"Tianjin University of Traditional Chinese Medicine","award":["No. 82204878"],"award-info":[{"award-number":["No. 82204878"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["No. 2021YFE0200300"],"award-info":[{"award-number":["No. 2021YFE0200300"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["No. 2020YFA0708004"],"award-info":[{"award-number":["No. 2020YFA0708004"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["No.YJSKC-20211015"],"award-info":[{"award-number":["No.YJSKC-20211015"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1027 A2"],"award-info":[{"award-number":["SFB 1027 A2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["No. 82204878"],"award-info":[{"award-number":["No. 82204878"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 2021YFE0200300"],"award-info":[{"award-number":["No. 2021YFE0200300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 2020YFA0708004"],"award-info":[{"award-number":["No. 2020YFA0708004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.YJSKC-20211015"],"award-info":[{"award-number":["No.YJSKC-20211015"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["SFB 1027 A2"],"award-info":[{"award-number":["SFB 1027 A2"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82204878"],"award-info":[{"award-number":["No. 82204878"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Natural killer (NK) cells play key roles in eliminating pathogen-infected cells. Verbena officinalis (V. officinalis) has been used as a medical plant in traditional and modern medicine for its anti-tumor and anti-inflammatory activities, but its effects on immune responses remain largely elusive. This study aimed to investigate the potential of V. officinalis extract (VO extract) to regulate inflammation and NK cell functions. We examined the effects of VO extract on lung injury in a mouse model of influenza virus infection. We also investigated the impact of five bioactive components of VO extract on NK killing functions using primary human NK cells. Our results showed that oral administration of VO extract reduced lung injury, promoted the maturation and activation of NK cells in the lung, and decreased the levels of inflammatory cytokines (IL-6, TNF-\u03b1 and IL-1\u03b2) in the serum. Among five bioactive components of VO extract, Verbenalin significantly enhanced NK killing efficiency in vitro, as determined by real-time killing assays based on plate-reader or high-content live-cell imaging in 3D using primary human NK cells. Further investigation showed that treatment of Verbenalin accelerated the killing process by reducing the contact time of NK cells with their target cells without affecting NK cell proliferation, expression of cytotoxic proteins, or lytic granule degranulation. Together, our findings suggest that VO extract has a satisfactory anti-inflammatory effect against viral infection in vivo, and regulates the activation, maturation, and killing functions of NK cells. Verbenalin from V. officinalis enhances NK killing efficiency, suggesting its potential as a promising therapeutic to fight viral infection.<\/jats:p>","DOI":"10.3390\/ijms24087144","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T02:29:15Z","timestamp":1681352955000},"page":"7144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Bioactive Constituents of Verbena officinalis Alleviate Inflammation and Enhance Killing Efficiency of Natural Killer Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Xiangdong","family":"Dai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangda","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Shao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana K.","family":"Yanamandra","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, 66421 Homburg, Germany"},{"name":"Leibniz Institute for New Materials, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimei","family":"Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute for Immunology, School of Medicine, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9085-1997","authenticated-orcid":false,"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3676-9183","authenticated-orcid":false,"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9382-3203","authenticated-orcid":false,"given":"Bin","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9633-9073","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kubica, P., Szopa, A., Kokotkiewicz, A., Miceli, N., Taviano, M.F., Maugeri, A., Cirmi, S., Synowiec, A., Gniewosz, M., and Elansary, H.O. (2020). Production of Verbascoside, Isoverbascoside and Phenolic Acids in Callus, Suspension, and Bioreactor Cultures of Verbena officinalis and Biological Properties of Biomass Extracts. Molecules, 25.","DOI":"10.3390\/molecules25235609"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.3389\/fphar.2016.00499","article-title":"Anticonvulsant, Anxiolytic, and Sedative Activities of Verbena officinalis","volume":"7","author":"Khan","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_3","first-page":"1241","article-title":"Verbena officinalis (Common Vervain)\u2014A Review on the Investigations of This Medicinally Important Plant Species","volume":"86","author":"Kubica","year":"2011","journal-title":"Planta Medica"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1080\/14786419.2017.1286477","article-title":"Production of verbascoside and phenolic acids in biomass of Verbena officinalis L. (vervain) cultured under different in vitro conditions","volume":"31","author":"Kubica","year":"2017","journal-title":"Nat. Prod. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10473","DOI":"10.3390\/molecules190710473","article-title":"Two New Iridoids from Verbena officinalis L","volume":"19","author":"Shu","year":"2014","journal-title":"Molecules"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11130-008-0073-0","article-title":"Antioxidant and Antifungal Activity of Verbena officinalis L. Leaves","volume":"63","author":"Casanova","year":"2008","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/j.1742-481X.2012.01114.x","article-title":"Effects of potassium apigenin and verbena extract on the wound healing process of SKH-1 mouse skin","volume":"11","author":"Castillo","year":"2014","journal-title":"Int. Wound J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1055\/s-2007-967116","article-title":"Effects of differential extraction of Verbena officinalis on rat models of inflammation, cicatrization and gastric damage","volume":"73","author":"Speroni","year":"2007","journal-title":"Planta Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/ni1322","article-title":"Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1","volume":"7","author":"Gazit","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.mad.2008.01.003","article-title":"Characterization of age-related changes in natural killer cells during primary influenza infection in mice","volume":"129","author":"Nogusa","year":"2008","journal-title":"Mech. Ageing Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.4049\/jimmunol.136.4.1435","article-title":"In vivo treatment of mice and hamsters with antibodies to asialo GM1 increases morbidity and mortality to pulmonary influenza infection","volume":"136","author":"Guffee","year":"1986","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/eji.201242620","article-title":"NK cells exacerbate the pathology of influenza virus infection in mice","volume":"43","author":"Zhou","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/infdis\/jis340","article-title":"Critical Role of Natural Killer Cells in Lung Immunopathology During Influenza Infection in Mice","volume":"206","author":"Mian","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s41586-022-04421-w","article-title":"The cGAS-STING pathway drives type I IFN immunopathology in COVID-19","volume":"603","author":"Domizio","year":"2022","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"644678","DOI":"10.3389\/fmed.2021.644678","article-title":"Human-Based Advanced in vitro Approaches to Investigate Lung Fibrosis and Pulmonary Effects of COVID-19","volume":"8","author":"Kiener","year":"2021","journal-title":"Front. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2515690X19853264","DOI":"10.1177\/2515690X19853264","article-title":"Evaluation of the Antispasmodic and Antisecretory Activities of the 80% Methanol Extracts of Verbena officinalis L: Evidence From In Vivo Antidiarrheal Study","volume":"24","author":"Sisay","year":"2019","journal-title":"J. Evid.-Based Integr. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5488","DOI":"10.1182\/blood-2008-10-187179","article-title":"Maturation of mouse NK cells is a 4-stage developmental program","volume":"113","author":"Laura","year":"2009","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1046\/j.1365-2567.1999.00738.x","article-title":"CD69 is a stimulatory receptor for natural killer cell and its cytotoxic effect is blocked by CD94 inhibitory receptor","volume":"97","author":"Borrego","year":"1999","journal-title":"Immunology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1002\/eji.201444518","article-title":"A simple, economic, time-resolved killing assay","volume":"44","author":"Kummerow","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16348","DOI":"10.1074\/jbc.RA118.004549","article-title":"Natural killer cells induce distinct modes of cancer cell death: Discrimination, quantification, and modulation of apoptosis, necrosis, and mixed forms","volume":"293","author":"Backes","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bhat, R., and Watzl, C. (2007). Serial Killing of Tumor Cells by Human Natural Killer Cells\u2014Enhancement by Therapeutic Antibodies. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000326"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1084\/jem.20181454","article-title":"NK cells switch from granzyme B to death receptor-mediated cytotoxicity during serial killing","volume":"216","author":"Prager","year":"2019","journal-title":"Exp Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/HNP.0b013e3181c8e4fe","article-title":"An integrative approach to rhinosinusitis in children, part II","volume":"24","author":"Ross","year":"2010","journal-title":"Holist. Nurs. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100489","DOI":"10.1016\/j.imr.2020.100489","article-title":"Efficacy of herbal medicine (Xuanfei Baidu decoction) combined with conventional drug in treating COVID-19:A pilot randomized clinical trial","volume":"9","author":"Xiong","year":"2020","journal-title":"Integr. Med. Res."},{"key":"ref_25","first-page":"422","article-title":"CD8 T cell responses to influenza virus infection in aged mice","volume":"10","author":"Jiang","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tian, X., Eikmans, M., and van der Hoorn, M.-L. (2020). The Role of Macrophages in Oocyte Donation Pregnancy: A Systematic Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030939"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1111\/j.1349-7006.2008.00763.x","article-title":"Inflammation and cancer: Role of nuclear factor-kappaB activation","volume":"99","author":"Maeda","year":"2008","journal-title":"Cancer Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.ijbiomac.2018.02.058","article-title":"Lectin obtained from the red seaweed Bryothamnion triquetrum: Secondary structure and anti-inflammatory activity in mice","volume":"112","author":"Fontenelle","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_29","first-page":"cm1","article-title":"Interleukin-1 (IL-1) Pathway","volume":"3","author":"Weber","year":"2010","journal-title":"Sci. Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"H32","DOI":"10.1152\/ajpheart.00569.2019","article-title":"Lactobacillus reuteri attenuates cardiac injury without lowering cholesterol in low-density lipoprotein receptor-deficient mice fed standard chow","volume":"319","author":"Koppinger","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.intimp.2010.04.013","article-title":"Betulinic acid isolated from Bacopa monniera (L.) Wettst suppresses lipopolysaccharide stimulated interleukin-6 production through modulation of nuclear factor-kappaB in peripheral blood mononuclear cells","volume":"10","author":"Viji","year":"2010","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","first-page":"4","article-title":"Effect of total glucosides of Verbena officinalis L. on rat model for chronic nonbacterial prostatitis","volume":"13","author":"Wang","year":"2016","journal-title":"China Med. Herald."},{"key":"ref_33","first-page":"23","article-title":"Effects of Verbenalin on Airway Inflammation, Airway Smooth Muscle Cell Proliferation and RhoA Expression in Rats with Bronchial Asthma Through NF-\u03baB\/MAPK Signaling Pathway","volume":"27","author":"Dong","year":"2021","journal-title":"Guid. J. Tradit. Chin. Med. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/JLB.MR0718-269R","article-title":"Mechanisms of natural killer cell-mediated cellular cytotoxicity","volume":"105","author":"Prager","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/nri2381","article-title":"Formation and function of the lytic NK-cell immunological synapse","volume":"8","author":"Orange","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/icb.2010.78","article-title":"Activating and inhibitory receptors of natural killer cells","volume":"89","author":"Pegram","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/83130","article-title":"On guard--activating NK cell receptors","volume":"2","author":"Lanier","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41423-019-0206-4","article-title":"Human NK cells: Surface receptors, inhibitory checkpoints, and translational applications","volume":"16","author":"Sivori","year":"2019","journal-title":"Cell. Mol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.4049\/jimmunol.1000761","article-title":"Tethering of Intercellular Adhesion Molecule on Target Cells Is Required for LFA-1\u2013Dependent NK Cell Adhesion and Granule Polarization","volume":"185","author":"Gross","year":"2010","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1091\/mbc.e09-11-0930","article-title":"Rapid Lytic Granule Convergence to the MTOC in Natural Killer Cells Is Dependent on Dynein But Not Cytolytic Commitment","volume":"21","author":"Mentlik","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6894","DOI":"10.4049\/jimmunol.1003471","article-title":"Docking of Lytic Granules at the Immunological Synapse in Human CTL Requires Vti1b-Dependent Pairing with CD3 Endosomes","volume":"186","author":"Qu","year":"2011","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1073\/pnas.1218640110","article-title":"An initial and rapid step of lytic granule secretion precedes microtubule organizing center polarization at the cytotoxic T lymphocyte\/target cell synapse","volume":"110","author":"Bertrand","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"867098","DOI":"10.3389\/fimmu.2022.867098","article-title":"Escaping Death: How Cancer Cells and Infected Cells Resist Cell-Mediated Cytotoxicity","volume":"13","author":"Tuomela","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41419-021-04227-0","article-title":"Sitagliptin activates the p62\u2013Keap1\u2013Nrf2 signalling pathway to alleviate oxidative stress and excessive autophagy in severe acute pancreatitis-related acute lung injury","volume":"12","author":"Kong","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/00000658-199201000-00007","article-title":"A Better Model of Acute Pancreatitis for Evaluating Therapy","volume":"215","author":"Schmidt","year":"1992","journal-title":"Ann. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0002-9440(10)63953-3","article-title":"Fas (CD95) Induces Alveolar Epithelial Cell Apoptosis in Vivo: Implications for Acute Pulmonary Inflammation","volume":"158","author":"Winn","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"729820","DOI":"10.3389\/fimmu.2021.729820","article-title":"Targeting the Microtubule-Network Rescues CTL Killing Efficiency in Dense 3D Matrices","volume":"12","author":"Zhao","year":"2021","journal-title":"Front. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7144\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:14:43Z","timestamp":1760123683000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,12]]},"references-count":47,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24087144"],"URL":"https:\/\/doi.org\/10.3390\/ijms24087144","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,12]]}}}