{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:17:34Z","timestamp":1785403054708,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation (Deutsche Forschungsgemeinschaft","award":["HE 6092\/2-1"],"award-info":[{"award-number":["HE 6092\/2-1"]}]},{"award":["HE 6092\/2-1"],"award-info":[{"award-number":["HE 6092\/2-1"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"German Centre for Cardiovascular Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/031t5w623","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010578","name":"Deutsche Gesellschaft f\u00fcr Kardiologie","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010578","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02p22ad51","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Charit\u00e9-Universitaetsmedizin Berlin and the Berlin Institute of Health"},{"id":[{"id":"https:\/\/ror.org\/0493xsw21","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Inactive rhomboid protein 2 (iRhom2) regulates ADAM17-mediated shedding of tumor necrosis factor-\u03b1 (TNF-\u03b1) from immune cells. We previously showed that iRhom2 deficiency attenuates early atherosclerosis in mice. This study aimed to characterize the impact of iRhom2 deficiency on macrophage phenotype and function. Bone marrow-derived macrophages (BMDMs) from iRhom2\u2212\/\u2212 and iRhom2+\/+ mice were analyzed for proliferation, phagocytosis, survival of cytotoxic stress, and polarization. Cytokine secretion after LPS stimulation was quantified, and iRhom2 expression under atherogenic stimuli was assessed. Conditioned media from BMDMs (BMDMcM) were applied to human aortic endothelial cells (HAoECs) to evaluate adhesion molecule expression and monocyte adhesion. iRhom2 deficiency did not affect BMDM proliferation, phagocytosis, survival, or polarization marker expression. iRhom2 expression was upregulated in iRhom2+\/+ BMDMs by atherogenic stimulation. Following LPS stimulation, TNF-\u03b1 secretion was decreased and IL-10 secretion was increased in iRhom2\u2212\/\u2212 compared with iRhom2+\/+ BMDMs. HAoEC expression of adhesion molecules\u2014ICAM-1, VCAM-1, and E-selectin\u2014was attenuated after exposure to iRhom2\u2212\/\u2212 compared with iRhom2+\/+ BMDMcM. Monocyte adhesion to HAoECs was reduced following treatment with iRhom2\u2212\/\u2212 BMDMcM; TNF-\u03b1 neutralization abolished this effect, indicating TNF-\u03b1 dependency. iRhom2 deficiency in BMDMs selectively alters macrophage inflammatory cytokine secretion without affecting basal macrophage functions, thereby reducing endothelial activation and monocyte adhesion. These findings identify iRhom2 as a regulator of macrophage\u2013endothelial crosstalk and a potential target to modulate inflammation in atherogenesis.<\/jats:p>","DOI":"10.3390\/biology15110860","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:08:02Z","timestamp":1780535282000},"page":"860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deficiency of Inactive Rhomboid Protein 2 (iRhom2) Attenuates Macrophage Atherogenicity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-0152","authenticated-orcid":false,"given":"Carmen","family":"Hannemann","sequence":"first","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alica","family":"Brettschneider","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"van Dijck","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Stangl","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8369-7020","authenticated-orcid":false,"given":"Antje","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3734-2533","authenticated-orcid":false,"given":"Bernd","family":"Hewing","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"},{"name":"Zentrum f\u00fcr Kardiologie, Kardiologische Gemeinschaftspraxis, 48143 Muenster, Germany"},{"name":"Department of Cardiology III\u2014Adult Congenital and Valvular Heart Disease, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/ATVBAHA.108.179705","article-title":"Inflammation in Atherosclerosis","volume":"32","author":"Libby","year":"2012","journal-title":"Arterioscler. 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