IQGAP2 regulates blood-brain barrier immune dynamics.
العنوان: | IQGAP2 regulates blood-brain barrier immune dynamics. |
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المؤلفون: | Katdare KA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA., Kjar A; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA., O'Brown NM; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Neal EH; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Sorets AG; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA., Shostak A; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA., Romero-Fernandez W; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA., Kwiatkowski AJ; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Mlouk K; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Kim H; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Cowell RP; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Schwensen KR; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Horner KB; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Wilson JT; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Schrag MS; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA., Megason SG; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Lippmann ES; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA. |
المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 12. Date of Electronic Publication: 2024 Apr 12. |
نوع المنشور: | Preprint |
اللغة: | English |
بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
مستخلص: | Brain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry of leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration of immune cells across the BBB is influenced by the scaffold protein IQ motif containing GTPase activating protein 2 (IQGAP2). In mice and zebrafish, we demonstrate that loss of Iqgap2 increases infiltration of peripheral leukocytes into the CNS under homeostatic and inflammatory conditions. Using single-cell RNA sequencing and immunohistology, we further show that BECs from mice lacking Iqgap2 exhibit a profound inflammatory signature, including extensive upregulation of adhesion receptors and antigen-processing machinery. Human tissue analyses also reveal that Alzheimer's disease is associated with reduced hippocampal IQGAP2. Overall, our results implicate IQGAP2 as an essential regulator of BBB immune privilege and immune cell entry into the CNS. Competing Interests: Competing interests The authors declare no competing interests. |
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معلومات مُعتمدة: | P30 DK058404 United States DK NIDDK NIH HHS; G20 RR030956 United States RR NCRR NIH HHS; P30 EY008126 United States EY NEI NIH HHS; S10 RR027396 United States RR NCRR NIH HHS; P30 DK020593 United States DK NIDDK NIH HHS; P30 CA068485 United States CA NCI NIH HHS; UL1 RR024975 United States RR NCRR NIH HHS; R21 NS106510 United States NS NINDS NIH HHS |
تواريخ الأحداث: | Date Created: 20240422 Latest Revision: 20240429 |
رمز التحديث: | 20240429 |
مُعرف محوري في PubMed: | PMC11030232 |
DOI: | 10.1101/2023.02.07.527394 |
PMID: | 38645082 |
قاعدة البيانات: | MEDLINE |
DOI: | 10.1101/2023.02.07.527394 |
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