Regulation of T cell afferent lymphatic migration by targeting LTβR-mediated non-classical NFκB signaling
Date
2018Journal
Nature CommunicationsPublisher
Nature Publishing GroupType
Article
Metadata
Show full item recordOther Titles
Regulation of T cell afferent lymphatic migration by targeting lymphotoxin-beta receptor-mediated non-classical NFκB signalingAbstract
Lymphotoxin-beta receptor (LTβR) signaling in lymphatic endothelial cells (LEC) regulates leukocyte afferent lymphatic transendothelial migration (TEM). The function of individual signaling pathways for different leukocyte subsets is currently unknown. Here, we show that LTβR signals predominantly via the constitutive and ligand-driven non-classical NIK pathway. Targeting LTβR-NIK by an LTβR-derived decoy peptide (nciLT) suppresses the production of chemokines CCL21 and CXCL12, and enhances the expression of classical NFκB-driven VCAM-1 and integrin β4 to retain T cells on LEC and precludes T cell and dendritic cell TEM. nciLT inhibits contact hypersensitivity (CHS) at both the sensitization and elicitation stages, likely by inhibiting leukocyte migration. By contrast, targeting LTβR-classical NFκB signaling during the elicitation and resolution stages attenuates CHS, possibly by promoting leukocyte egress. These findings demonstrate the importance of LTβR signaling in leukocyte migration and LEC and lymphatic vessel function, and show that antagonist peptides may serve as lead compounds for therapeutic applications. Copyright 2018, The Author(s).Description
Author Correction for this article is at https://www.doi.org/10.1038/s41467-019-10952-0.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85050989714&doi=10.1038%2fs41467-018-05412-0&partnerID=40&md5=33b5cde07b4d709dd9c52f49982874f1; http://hdl.handle.net/10713/9451ae974a485f413a2113503eed53cd6c53
10.1038/s41467-018-05412-0
Scopus Count
Collections
Related articles
- Regulatory T Cells Condition Lymphatic Endothelia for Enhanced Transendothelial Migration.
- Authors: Piao W, Xiong Y, Li L, Saxena V, Smith KD, Hippen KL, Paluskievicz C, Willsonshirkey M, Blazar BR, Abdi R, Bromberg JS
- Issue date: 2020 Jan 28
- Lymphotoxin-β receptor activation by lymphotoxin-α(1)β(2) and LIGHT promotes tumor growth in an NFκB-dependent manner.
- Authors: Daller B, Müsch W, Röhrl J, Tumanov AV, Nedospasov SA, Männel DN, Schneider-Brachert W, Hehlgans T
- Issue date: 2011 Mar 15
- Lymphotoxin-alpha 1 beta 2 and LIGHT induce classical and noncanonical NF-kappa B-dependent proinflammatory gene expression in vascular endothelial cells.
- Authors: Madge LA, Kluger MS, Orange JS, May MJ
- Issue date: 2008 Mar 1
- Lymphotoxin β receptor-mediated NFκB signaling promotes glial lineage differentiation and inhibits neuronal lineage differentiation in mouse brain neural stem/progenitor cells.
- Authors: Xiao X, Putatunda R, Zhang Y, Soni PV, Li F, Zhang T, Xin M, Luo JJ, Bethea JR, Cheng Y, Hu W
- Issue date: 2018 Feb 20
- Mouse aorta smooth muscle cells differentiate into lymphoid tissue organizer-like cells on combined tumor necrosis factor receptor-1/lymphotoxin beta-receptor NF-kappaB signaling.
- Authors: Lötzer K, Döpping S, Connert S, Gräbner R, Spanbroek R, Lemser B, Beer M, Hildner M, Hehlgans T, van der Wall M, Mebius RE, Lovas A, Randolph GJ, Weih F, Habenicht AJ
- Issue date: 2010 Mar