Human CD4 + T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro
Hideaki Nishihara,Sasha Soldati,Adrien Mossu,Maria Rosito,Maria Rosito,Henriette Rudolph,William A. Muller,Daniela Latorre,Daniela Latorre,Federica Sallusto,Federica Sallusto,Mireia Sospedra,Roland Martin,Hiroshi Ishikawa,Tobias Tenenbaum,Horst Schroten,Fabien Gosselet,Britta Engelhardt +17 more
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TLDR
Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4+ T-cell subsets across the BBB versus the BCSFB indicates that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation.Abstract:
The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood–brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP). Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4+ T-cell subsets across the BBB versus the BCSFB. Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4+ T helper cell subsets (Th1, Th1*, Th2, Th17) across the BBB and BCSFB under inflammatory and non-inflammatory conditions in vitro. While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration. Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB.read more
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In vitro modeling of blood–brain barrier and interface functions in neuroimmune communication
TL;DR: How conventional in vitro models of the BBB have improved the understanding of the 5 neuroimmune axes is discussed and the existing literature on neuroimmune functions of novel in vitro BBB models, such as those derived from human induced pluripotent stem cells (iPSCs), are evaluated and discussed.
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Advancing human induced pluripotent stem cell-derived blood-brain barrier models for studying immune cell interactions.
Hideaki Nishihara,Benjamin D. Gastfriend,Sasha Soldati,Sylvain Perriot,Amandine Mathias,Yasuteru Sano,Fumitaka Shimizu,Fabien Gosselet,Takashi Kanda,Sean P. Palecek,Renaud Du Pasquier,Eric V. Shusta,Britta Engelhardt +12 more
TL;DR: The extended endothelial cell culture method (EECM) is introduced, which differentiates hiPSC‐derived endothelial progenitor cells to brain microvascular endothelialcell (BMEC)‐like cells with good barrier properties and mature tight junctions and introduces the first hiPSc‐derived BBB model that displays an adhesion molecule phenotype that is suitable for the study of immune cell interactions.
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Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging
Yi Mou,Yu-zheng Du,Lixing Zhou,Jirong Yu,Xian-Liang Hu,Yixin Liu,Sao Chen,Xiufang Lin,Gongchang Zhang,Hengyi Xiao,Birong Dong +10 more
TL;DR: To add depth to the bridging role of systemic chronic inflammation, a plausible mechanism indispensable for BBB corruption was highlighted; namely, BBB maintenance cues are affected by inflammatory cytokines, which may help to understand how GM and its metabolites play a major role in NF&ND and aging.
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Drugs Modulating CD4+ T Cells Blood-Brain Barrier Interaction in Alzheimer's Disease.
TL;DR: Future drug design approaches should specifically consider inhibiting CD4+ Th17 to improve AD prognosis, and none of the current AD drugs is specifically designed to target the dysregulated balance in the Th17/Treg axis.
Journal ArticleDOI
Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood-brain barrier.
Mariana Castro Dias,Adolfo Odriozola Quesada,Sasha Soldati,Fabio Bösch,Isabelle Gruber,Tobias Hildbrand,Derya Sönmez,Tejas S. Khire,Guillaume Witz,James L. McGrath,Jörg Piontek,Masuo Kondoh,Urban Deutsch,Benoît Zuber,Britta Engelhardt +14 more
TL;DR: In this article, the authors used serial block-face scanning electron microscopy (SBF-SEM) to identify BBB tricellular junctions as novel sites for T cell diapedesis across the BBB.
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