163745 20240227115127.0 10.3389/fimmu.2022.824459 doi pmid:35281004 pmid pmc:PMC8907149 pmc altmetric:123582560 altmetric DZNE-2022-00484 English 610 Zhang, Jin 0 Fast Maturation of Splenic Dendritic Cells Upon TBI Is Associated With FLT3/FLT3L Signaling. Lausanne 2022 Frontiers Media article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1709024784_12962 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote The consequences of systemic inflammation are a significant burden after traumatic brain injury (TBI), with almost all organs affected. This response consists of inflammation and concurrent immunosuppression after injury. One of the main immune regulatory organs, the spleen, is highly interactive with the brain. Along this brain-spleen axis, both nerve fibers as well as brain-derived circulating mediators have been shown to interact directly with splenic immune cells. One of the most significant comorbidities in TBI is acute ethanol intoxication (EI), with almost 40% of patients showing a positive blood alcohol level (BAL) upon injury. EI by itself has been shown to reduce proinflammatory mediators dose-dependently and enhance anti-inflammatory mediators in the spleen. However, how the splenic immune modulatory effect reacts to EI in TBI remains unclear. Therefore, we investigated early splenic immune responses after TBI with and without EI, using gene expression screening of cytokines and chemokines and fluorescence staining of thin spleen sections to investigate cellular mechanisms in immune cells. We found a strong FLT3/FLT3L induction 3 h after TBI, which was enhanced by EI. The FLT3L induction resulted in phosphorylation of FLT3 in CD11c+ dendritic cells, which enhanced protein synthesis, maturation process, and the immunity of dendritic cells, shown by pS6, peIF2A, MHC-II, LAMP1, and CD68 by immunostaining and TNF-α expression by in-situ hybridization. In conclusion, these data indicate that TBI induces a fast maturation and immunity of dendritic cells which is associated with FLT3/FLT3L signaling and which is enhanced by EI prior to TBI. 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 1 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de FLT3 Other dendritic cell Other ethanol Other spleen Other traumatic brain injury Other Brain Injuries, Traumatic: metabolism MeSH Dendritic Cells MeSH Humans MeSH Inflammation MeSH Membrane Proteins: genetics MeSH Spleen MeSH fms-Like Tyrosine Kinase 3 MeSH Li, Zhenghui 1 Chandrasekar, Akila 2 Li, Shun 3 Ludolph, Albert P:(DE-2719)2812633 4 dzne Böckers, Tobias P:(DE-2719)2812855 5 dzne Huber-Lang, Markus 6 Roselli, Francesco P:(DE-2719)2812851 7 dzne Olde Heuvel, Florian 8 10.3389/fimmu.2022.824459 Vol. 13, p. 824459 PERI:(DE-600)2606827-8 824459 Frontiers in immunology 13 2022 1664-3224 http://pub.dzne.de/record/163745/files/DZNE-2022-00484.pdf OpenAccess http://pub.dzne.de/record/163745/files/DZNE-2022-00484.pdf?subformat=pdfa pdfa OpenAccess oai:pub.dzne.de:163745 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)2812633 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)2812855 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)2812851 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 1 2022 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2021-01-29 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2021-01-29 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2021-01-29 Fees StatID:(DE-HGF)0700 StatID 2021-01-29 OpenAccess StatID:(DE-HGF)0510 StatID Article Processing Charges StatID:(DE-HGF)0561 StatID 2021-01-29 JCR StatID:(DE-HGF)0100 StatID FRONT IMMUNOL : 2021 2022-11-23 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-23 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-23 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-05-11T10:28:02Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-05-11T10:28:02Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review 2021-05-11T10:28:02Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-23 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-23 IF >= 5 StatID:(DE-HGF)9905 StatID FRONT IMMUNOL : 2021 2022-11-23 I:(DE-2719)5000077 Clinical Study Center Ulm Clinical Study Center Ulm 0 I:(DE-2719)1910002 AG Böckers Translational Protein Biochemistry 1 I:(DE-2719)1910001 AG Roselli Metabolic Changes in Neurodegeneration 2 journal VDB I:(DE-2719)5000077 I:(DE-2719)1910002 I:(DE-2719)1910001 UNRESTRICTED FullTexts