Reglero-Real, N;
Perez-Gutierrez, L;
Yoshimura, A;
Rolas, L;
Garrido-Mesa, J;
Barkaway, A;
Pickworth, C;
... Nourshargh, S; + view all
(2021)
Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation.
Immunity
, 54
(9)
1989-2004.e9.
10.1016/j.immuni.2021.07.012.
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Abstract
The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation.
| Type: | Article |
|---|---|
| Title: | Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.immuni.2021.07.012 |
| Publisher version: | https://doi.org/10.1016/j.immuni.2021.07.012 |
| Language: | English |
| Additional information: | © 2021 The Author(s). Published by Elsevier Inc. 1989 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Immunology, TRANSENDOTHELIAL MIGRATION, VASCULAR-PERMEABILITY, IN-VIVO, JAM-C, MECHANISMS, PROTEIN, PECAM-1, PHAGOCYTOSIS, ASSOCIATION, DEFICIENCY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10142120 |
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