{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T16:06:43Z","timestamp":1778170003525,"version":"3.51.4"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T00:00:00Z","timestamp":1658016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-31859\/2017"],"award-info":[{"award-number":["POCI-01-0145-FEDER-31859\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["CANCER_CHALLENGE2022"],"award-info":[{"award-number":["CANCER_CHALLENGE2022"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto","award":["POCI-01-0145-FEDER-31859\/2017"],"award-info":[{"award-number":["POCI-01-0145-FEDER-31859\/2017"]}]},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto","award":["CANCER_CHALLENGE2022"],"award-info":[{"award-number":["CANCER_CHALLENGE2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>CD1d-restricted invariant Natural Killer T (iNKT) cells are unconventional innate-like T cells whose functions highly depend on the interactions they establish with other immune cells. Although extensive studies have been reported on the communication between iNKT cells and macrophages in mice, less data is available regarding the relevance of this crosstalk in humans. Here, we dove into the human macrophage-iNKT cell axis by exploring how iNKT cells impact the survival and polarization of pro-inflammatory M1-like and anti-inflammatory M2-like monocyte-derived macrophages. By performing in vitro iNKT cell-macrophage co-cultures followed by flow cytometry analysis, we demonstrated that antigen-stimulated iNKT cells induce a generalized activated state on all macrophage subsets, leading to upregulation of CD40 and CD86 expression. CD40L blocking with a specific monoclonal antibody prior to co-cultures abrogated CD40 and CD86 upregulation, thus indicating that iNKT cells required CD40-CD40L co-stimulation to trigger macrophage activation. In addition, activated iNKT cells were cytotoxic towards macrophages in a CD1d-dependent manner, killing M1-like macrophages more efficiently than their na\u00efve M0 or anti-inflammatory M2-like counterparts. Hence, this work highlighted the role of human iNKT cells as modulators of macrophage survival and phenotype, untangling key features of the human macrophage-iNKT cell axis and opening perspectives for future therapeutic modulation.<\/jats:p>","DOI":"10.3390\/biomedicines10071723","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T21:00:28Z","timestamp":1658091628000},"page":"1723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Human iNKT Cells Modulate Macrophage Survival and Phenotype"],"prefix":"10.3390","volume":"10","author":[{"given":"J. Pedro","family":"Loureiro","sequence":"first","affiliation":[{"name":"Cell Activation and Gene Expression Group, Institute for Molecular and Cell Biology (IBMC), Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Experimental Immunology Group, Department of Biomedicine (DBM), University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5959-7153","authenticated-orcid":false,"given":"Mariana S.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Cell Activation and Gene Expression Group, Institute for Molecular and Cell Biology (IBMC), Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Department of Medical Sciences, University of Aveiro (UA), 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-0316","authenticated-orcid":false,"given":"Ana P.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Tumour and Microenvironment Interactions Group, Institute of Biomedical Engineering (INEB), Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0724-0272","authenticated-orcid":false,"given":"Maria J.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Tumour and Microenvironment Interactions Group, Institute of Biomedical Engineering (INEB), Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2252-6105","authenticated-orcid":false,"given":"M. F\u00e1tima","family":"Macedo","sequence":"additional","affiliation":[{"name":"Cell Activation and Gene Expression Group, Institute for Molecular and Cell Biology (IBMC), Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Department of Medical Sciences, University of Aveiro (UA), 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/ni.1841","article-title":"Raising the NKT Cell Family","volume":"11","author":"Godfrey","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1146\/annurev-immunol-032414-112008","article-title":"The Immunology of CD1- and MR1-Restricted T Cells","volume":"34","author":"Mori","year":"2016","journal-title":"Annu. Rev. 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