{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:51:26Z","timestamp":1791165086172,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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>\n                      Asthma and obesity are highly prevalent chronic inflammatory diseases, the mutual pathomechanistic relationships of which have not been fully elucidated yet. We hypothesized that inflammatory mechanisms in obese adipose tissue influence the phenotype of an induced allergic airway inflammation (AAI) with altered activation processes in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells being involved in this interaction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      C57BL\/6 and BALB\/c mice were fed high\u2010fat (HFD) or normal (ND) diet for several weeks and subjected to a house dust mite (HDM)\u2010induced model of AAI mimicking main features of human asthma. Inflammatory and metabolic parameters were assessed and lung CD45\n                      <jats:sup>+<\/jats:sup>\n                      cells were deep\u2010phenotyped using flow cytometry and targeted single cell CITE\u2010Seq (cellular indexing of transcriptomes and epitopes by sequencing) analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Despite comparable metabolic changes in both strains in response to HFD, only C57BL\/6 mice developed excessive weight gain. In both strains, the chosen HDM exposure protocol induced a mixed AAI phenotype characterized by eosinophil and neutrophil airway infiltration in ND\u2010fed mice. However, only in C57BL\/6 mice, concomitant HFD resulted in changed eosinophils to neutrophils ratios and a higher proportion of lung CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Using single\u2010cell CITE\u2010Seq, a specific subcluster of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells was identified exclusively in the lungs of lean, but not in obese, HDM\u2010exposed C57BL\/6 mice, characterized by the expression of co\u2010inhibitory receptors such as CTLA\u20104, PD\u20101, and LAG\u20103. Furthermore, culturing pre\u2010differentiated T cells in the presence of supernatants from hypertrophic adipocytes resulted in reduced frequencies of cells expressing these receptors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The presence of co\u2010inhibitory receptor\u2010expressing CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells in lean mice with AAI may represent a disease\u2010limiting mechanism, which is abolished by a co\u2010existing obesity resulting in intensified inflammatory processes in the lungs. This mechanism could explain higher asthma severity observed in obese patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70492","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:55:55Z","timestamp":1791161755000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selective Absence of Co\u2010Inhibitory Receptor\u2010Expressing\n                    <scp>CD4<\/scp>\n                    <sup>+<\/sup>\n                    T Cells in Lungs of Obese House Dust Mite\u2010Allergic\n                    <scp>C57BL<\/scp>\n                    \/6 Mice"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7118-3279","authenticated-orcid":false,"given":"Sarah","family":"Miethe","sequence":"first","affiliation":[{"name":"Translational Inflammation Research Division &amp; Core Facility for Single Cell Multiomics Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center (UGMLC), Medical Faculty, Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0324-8506","authenticated-orcid":false,"given":"Daniel P.","family":"Potaczek","sequence":"additional","affiliation":[{"name":"Translational Inflammation Research Division &amp; Core Facility for Single Cell Multiomics Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center (UGMLC), Medical Faculty, Philipps University of Marburg  Marburg Germany"},{"name":"Center for Infection and Genomics of the Lung (CIGL) Member of the German Center for Lung Research (DZL) and Universities of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0756-0142","authenticated-orcid":false,"given":"Kim","family":"Pauck","sequence":"additional","affiliation":[{"name":"Translational Inflammation Research Division &amp; Core Facility for Single Cell Multiomics Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center (UGMLC), Medical Faculty, Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Berlin","sequence":"additional","affiliation":[{"name":"Translational Inflammation Research Division &amp; Core Facility for Single Cell Multiomics Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center (UGMLC), Medical Faculty, Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7120-0013","authenticated-orcid":false,"given":"Bilal Alashkar","family":"Alhamwe","sequence":"additional","affiliation":[{"name":"Center for Tumor Biology and Immunology (ZTI) Institute for Tumor Immunology, Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Hagner","sequence":"additional","affiliation":[{"name":"Translational Inflammation Research Division &amp; Core Facility for Single Cell Multiomics Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center (UGMLC), Medical Faculty, Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Nist","sequence":"additional","affiliation":[{"name":"Center for Tumor Biology and Immunology (ZTI) Institute of Molecular Oncology and Genomics Core Facility, Member of the German Center for Lung Research (DZL), Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4785-9165","authenticated-orcid":false,"given":"Elke Pogge","family":"von Strandmann","sequence":"additional","affiliation":[{"name":"Center for Tumor Biology and Immunology (ZTI) Institute for Tumor Immunology, Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0134-7826","authenticated-orcid":false,"given":"Thorsten","family":"Stiewe","sequence":"additional","affiliation":[{"name":"Center for Tumor Biology and Immunology (ZTI) Institute of Molecular Oncology and Genomics Core Facility, Member of the German Center for Lung Research (DZL), Philipps University of Marburg  Marburg Germany"},{"name":"Institute for Lung Health (ILH), Justus Liebig University of Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3609-5713","authenticated-orcid":false,"given":"Paul","family":"Klemm","sequence":"additional","affiliation":[{"name":"Center for Synthetic Microbiology (SYNMICRO)\u2014Bioinformatics Core Facility Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmann","family":"Raifer","sequence":"additional","affiliation":[{"name":"Center for Tumor Biology and Immunology (ZTI) Institute of Systems Immunology and Flow Cytometry Core Facility, Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4328-9193","authenticated-orcid":false,"given":"Clemens","family":"Th\u00f6lken","sequence":"additional","affiliation":[{"name":"Center for Synthetic Microbiology (SYNMICRO)\u2014Bioinformatics Core Facility Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5178-4023","authenticated-orcid":false,"given":"Holger","family":"Garn","sequence":"additional","affiliation":[{"name":"Translational Inflammation Research Division &amp; Core Facility for Single Cell Multiomics Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center (UGMLC), Medical Faculty, Philipps University of Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"L130","DOI":"10.1152\/ajplung.00070.2014","article-title":"Emerging Molecular Phenotypes of Asthma","volume":"308","author":"Ray A.","year":"2015","journal-title":"American Journal of Physiology. 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