{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:38:59Z","timestamp":1787776739249,"version":"build-2784847793"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2020\u201002170"],"award-info":[{"award-number":["2020\u201002170"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018861","name":"Konsul Th C Berghs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cytotoxic type 2 T cells (Tc2) are increasingly recognized as contributors to type 2 inflammation, including asthma, yet the metabolic programs that support their function remain poorly defined. We aimed to define the metabolic requirements of Tc2 cells, identify pathways that regulate their effector function, and assess whether serotonin\u2010modifying therapies are associated with altered Tc2 responses and allergic sensitization in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tc2 cells from human peripheral blood and lung tissue were analyzed using Seahorse metabolic assays, Mitotracker staining, flow cytometry, and RNA sequencing. Effector functions were evaluated following inhibition of glycolysis, fatty acid metabolism, and monoamine oxidase A (MAOA) inhibition. In parallel, anti\u2010depressant prescription data were analyzed in the population\u2010based BAMSE cohort to assess associations with allergic sensitization. Peripheral blood mononuclear cells from individuals prescribed selective serotonin reuptake inhibitors (SSRIs) and matched controls were stimulated ex\u00a0vivo to assess cytokine production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tc2 cells exhibited a distinct metabolic profile characterized by increased mitochondrial respiration, glycolytic activity, and elevated expression of GLUT1 and CD36. Type 2 cytokine production (IL\u20104, IL\u20105, IL\u201013) was enhanced by alarmins and significantly reduced following inhibition of glycolysis, fatty acid metabolism, or PPAR\u03b3 activity. RNA sequencing identified high MAOA expression in Tc2 cells, and pharmacological inhibition of MAOA selectively reduced type 2 cytokine production without affecting IFN\u2010\u03b3. In the BAMSE cohort, dispensing of prescribed anti\u2010depressive drugs was associated with reduced IgE sensitization. Consistent with these findings, individuals prescribed SSRIs exhibited reduced IL\u20105\n                      <jats:sup>+<\/jats:sup>\n                      and IL\u201013\n                      <jats:sup>+<\/jats:sup>\n                      expressing Tc2 cells and increased IFN\u2010\u03b3\u2013producing Tc2 cells following ex\u00a0vivo stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tc2 cells rely on coordinated lipid metabolism and serotonin catabolism to sustain type 2 cytokine production. Serotonin\u2010modifying therapies were associated with reduced allergic sensitization and altered Tc2 function in humans, consistent with a link between serotonin signaling and type 2 immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70399","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:40:14Z","timestamp":1782916814000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serotonin Degradation and Lipid Metabolism Regulate Human Tc2 Cell Effector Functions"],"prefix":"10.1111","author":[{"given":"Sabrina","family":"de Souza Ferreira","sequence":"first","affiliation":[{"name":"Centre for Infectious Medicine, Department of Medicine Huddinge Karolinska Institutet and Karolinska University Hospital  Stockholm Sweden"},{"name":"Clinical Lung\u2010 and Allergy Research Unit, Department of Medicine Huddinge Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5460-2765","authenticated-orcid":false,"given":"Lisa","family":"Holla","sequence":"additional","affiliation":[{"name":"Centre for Infectious Medicine, Department of Medicine Huddinge Karolinska Institutet and Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Bj\u00f6rkander","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education S\u00f6dersjukhuset, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Kaarup","family":"Bek","sequence":"additional","affiliation":[{"name":"Centre for Infectious Medicine, Department of Medicine Huddinge Karolinska Institutet and Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Wirth","sequence":"additional","affiliation":[{"name":"Centre for Infectious Medicine, Department of Medicine Huddinge Karolinska Institutet and Karolinska University Hospital  Stockholm Sweden"},{"name":"Clinical Lung\u2010 and Allergy Research Unit, Department of Medicine Huddinge Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A.","family":"Shearer","sequence":"additional","affiliation":[{"name":"Centre for Infectious Medicine, Department of Medicine Huddinge Karolinska Institutet and Karolinska University Hospital  Stockholm Sweden"},{"name":"Clinical Lung\u2010 and Allergy Research Unit, Department of Medicine Huddinge Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1922-8104","authenticated-orcid":false,"given":"Jesper","family":"S\u00e4fholm","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Sachs","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Surgery, MMK Thoracic Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamdoh","family":"Al\u2010Ameri","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Surgery, MMK Thoracic Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasra","family":"Vali","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Surgery, MMK Thoracic Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2060-8190","authenticated-orcid":false,"given":"Sandra","family":"Ekstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education S\u00f6dersjukhuset, Karolinska Institutet  Stockholm Sweden"},{"name":"Institute of Environmental Medicine Karolinska Institutet  Stockholm Sweden"},{"name":"Centre for Occupational and Environmental Medicine Region Stockholm  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8248-0663","authenticated-orcid":false,"given":"Erik","family":"Mel\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education S\u00f6dersjukhuset, Karolinska Institutet  Stockholm Sweden"},{"name":"Sachs' Children and Youth Hospital S\u00f6dersjukhuset  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Mj\u00f6sberg","sequence":"additional","affiliation":[{"name":"Centre for Infectious Medicine, Department of Medicine Huddinge Karolinska Institutet and Karolinska University Hospital  Stockholm Sweden"},{"name":"Clinical Lung\u2010 and Allergy Research Unit, Department of Medicine Huddinge Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7730-7700","authenticated-orcid":false,"given":"Christopher Andrew","family":"Tibbitt","sequence":"additional","affiliation":[{"name":"Centre for Infectious Medicine, Department of Medicine Huddinge Karolinska Institutet and Karolinska University Hospital  Stockholm Sweden"},{"name":"Clinical Lung\u2010 and Allergy Research Unit, Department of Medicine Huddinge Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2992"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1996.tb00646.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.018"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1221064"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.118"},{"key":"e_1_2_11_7_1","first-page":"6","article-title":"TCR Signal Strength Alters T\u2010DC Activation and Interaction Times and Directs the Outcome of Differentiation","volume":"7","author":"Panhuys N.","year":"2016","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0092-2019"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-018-0049-9"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40820-x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.04.005"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02318"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-021-01022-x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.12.004"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00879"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2024.102500"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.645242"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-023-03622-0"},{"key":"e_1_2_11_19_1","first-page":"100","article-title":"Beyond a Neurotransmitter: The Role of Serotonin in Inflammation and Immunity","volume":"140","author":"Wu H.","year":"2019","journal-title":"Serotonin Brain"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abh2383"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-052787"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-019-0126-x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-00996-0"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.12.015"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.05.006"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3038.13.s.15.10.x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13601-020-00319-w"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-025-22522-9"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02120-2020"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1294"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15728"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3244"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00704-5"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2017.00048"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106922"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.2002.tb00229.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852922000906"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16633"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201406-1039OC"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201903-0588OC"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38233-x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13683"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18565-8"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.05.014"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3582"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.876515"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11071105"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215753"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.003"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15609"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151448"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.858051"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00595-9"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545473"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847525"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-024-05570-z"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn300186b"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.169613"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113433"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14791"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.09.012"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.04.030"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abc9089"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-00982-6"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-26296-7"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70399","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.70399","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:10:10Z","timestamp":1783944610000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.70399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":64,"alternative-id":["10.1111\/all.70399"],"URL":"https:\/\/doi.org\/10.1111\/all.70399","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"assertion":[{"value":"2025-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"all.70399"}}