Regulation of T cell afferent lymphatic migration by targeting LTßR-mediated non-classical NFκB signaling.
Nat Commun
; 9(1): 3020, 2018 08 01.
Article
en En
| MEDLINE
| ID: mdl-30069025
ABSTRACT
Lymphotoxin-beta receptor (LTßR) 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 LTßR signals predominantly via the constitutive and ligand-driven non-classical NIK pathway. Targeting LTßR-NIK by an LTßR-derived decoy peptide (nciLT) suppresses the production of chemokines CCL21 and CXCL12, and enhances the expression of classical NFκB-driven VCAM-1 and integrin ß4 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 LTßR-classical NFκB signaling during the elicitation and resolution stages attenuates CHS, possibly by promoting leukocyte egress. These findings demonstrate the importance of LTßR signaling in leukocyte migration and LEC and lymphatic vessel function, and show that antagonist peptides may serve as lead compounds for therapeutic applications.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T
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Transducción de Señal
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Movimiento Celular
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FN-kappa B
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Vasos Linfáticos
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Receptor beta de Linfotoxina
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2018
Tipo del documento:
Article