{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:27:25Z","timestamp":1784590045708,"version":"3.55.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"PREADAPT project","award":["01ED2007B"],"award-info":[{"award-number":["01ED2007B"]}]},{"DOI":"10.13039\/501100000780","name":"EU","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuroinflammation plays a vital role in determining the trajectory of Alzheimer's disease (AD) progression. In the AD brain, microglial exposure to pathological amyloid \u03b2 (A\u03b242) and tau peptide aggregates results in an NLRP3 inflammasome\u2013activated proinflammatory response that ranges from mild to severe. Recently we have shown that dementia subjects with higher levels of soluble TAM receptors Tyro3 and AXL in the cerebrospinal fluid indicated cognitive protection. The molecular mechanism for this protective effect of TAM receptors is unknown. Here, we identified a beneficial role of TAM receptors using Tyro3-overexpressing (Tyro3OE) and Axl-overexpressing THP-1 cells. In the Tyro3OE cells, the levels of the proinflammatory cytokine IL-1\u03b2 were markedly decreased in the AD microenvironment (tau + A\u03b242) and the classical NLRP3 inflammasome model (lipopolysaccharide [LPS] + nigericin) in comparison with the control cells. This was mediated by increased STAT1 phosphorylation and reduced IL-1\u03b2 transcription enhancer C-EBP-\u03b2 in Tyro3OE cells. The use of the JAK1\/2 inhibitor ruxolitinib reduced the phosphorylation of STAT1, leading to a partial restoration of IL-1\u03b2 in the Tyro3OE cells. Last, we found a significantly reduced IL-1\u03b2 in the brains of AD mice that has activated TAM signaling through Gas6-\u03b1-A\u03b2 lentiviral injection. In summary, TAM receptor Tyro3 overexpression decreased AD-associated IL-1\u03b2 release from macrophages thereby uncovering a potential beneficial role for TAM receptors during neuroinflammation in AD.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf157","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:21:03Z","timestamp":1762647663000},"source":"Crossref","is-referenced-by-count":2,"title":["Enhancing Tyro3 signaling ameliorates IL-1\u03b2 production through STAT1 in Alzheimer's disease models"],"prefix":"10.1093","volume":"117","author":[{"given":"Kishore Aravind","family":"Ravichandran","sequence":"first","affiliation":[{"name":"Department of Neuroimmunology, Institute of Innate Immunity, University Hospital Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]},{"name":"German Centre for Neurodegenerative Diseases (DZNE) Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]},{"name":"Institute for Neurovascular Cell Biology, University Hospital Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Brosseron","sequence":"additional","affiliation":[{"name":"German Centre for Neurodegenerative Diseases (DZNE) Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]},{"name":"Department of Neurodegenerative disease and Geriatric Psychiatry, University Hospital Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00f3is\u00edn M","family":"McManus","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Institute of Innate Immunity, University Hospital Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]},{"name":"German Centre for Neurodegenerative Diseases (DZNE) Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Ising","sequence":"additional","affiliation":[{"name":"CECAD\u2013Cluster of Excellence, University of Cologne , Joseph-Stelzmann-Stra\u00dfe 26, 50931 Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"G\u00f6rgen","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Institute of Innate Immunity, University Hospital Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne V","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Institute of Innate Immunity, University Hospital Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fracesco","family":"Santarelli","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Institute of Innate Immunity, University Hospital Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]},{"name":"German Centre for Neurodegenerative Diseases (DZNE) Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Korea, Korea Advanced Institute of Science and Technology , 291, Daehak-ro, Yuseong-gu, 34141 Daejeon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuncheol","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Korea, Korea Advanced Institute of Science and Technology , 291, Daehak-ro, Yuseong-gu, 34141 Daejeon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Suk","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Korea, Korea Advanced Institute of Science and Technology , 291, Daehak-ro, Yuseong-gu, 34141 Daejeon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Hyuk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Korea, Korea Advanced Institute of Science and Technology , 291, Daehak-ro, Yuseong-gu, 34141 Daejeon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"Ruiz Laza","sequence":"additional","affiliation":[{"name":"Research Centre and Memory Clinic, ACE Alzheimer Centre, Universitat Internacional de Catalunya , C\/ Gran Via de Carles III, 85 bis, 08028 Barcelona ,","place":["Spain"]},{"name":"Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III , C\/ Monforte de Lemos, 3-5. Pabell\u00f3n 11, Planta 0, Fuencarral-El Pardo, 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Ruiz de Almod\u00f3var","sequence":"additional","affiliation":[{"name":"Institute for Neurovascular Cell Biology, University Hospital Bonn , Venusberg-Campus 1, 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-763X","authenticated-orcid":false,"given":"Alfredo","family":"Ramirez","sequence":"additional","affiliation":[{"name":"CECAD\u2013Cluster of Excellence, University of Cologne , Joseph-Stelzmann-Stra\u00dfe 26, 50931 Cologne ,","place":["Germany"]},{"name":"Neurogenetics and Molecular Psychiatry, CECAD, University of Cologne , Joseph-Stelzmann-Stra\u00dfe 26, 50931 Cologne 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