TNFα promotes CAR-dependent migration of leukocytes across epithelial monolayers
TNFα promotes CAR-dependent migration of leukocytes across epithelial monolayers
Trans-epithelial migration (TEpM) of leukocytes during inflammation requires engagement with receptors expressed on the basolateral surface of the epithelium. One such receptor is Coxsackie and Adenovirus Receptor (CAR) that binds to Junctional Adhesion Molecule-like (JAM-L) expressed on leukocytes. Here we provide the first evidence that efficient TEpM of monocyte-derived THP-1 cells requires and is controlled by phosphorylation of CAR. We show that TNFα acts in a paracrine manner on epithelial cells via a TNFR1-PI3K-PKCδ pathway leading to CAR phosphorylation and subsequent transmigration across cell junctions. Moreover, we show that CAR is hyper-phosphorylated in vivo in acute and chronic lung inflammation models and this response is required to facilitate immune cell recruitment. This represents a novel mechanism of feedback between leukocytes and epithelial cells during TEpM and may be important in controlling responses to pro-inflammatory cytokines in pathological settings.
Morton, Penny
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Hicks, Alexander
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Ortiz-Zapater, Elena
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Raghavan, Swetavalli
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Pike, Rosemary
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Noble, Alistair
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Woodfin, Abigail
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Jenkins, Gisli
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Rayner, Emma
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Santis, George
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Parsons, Maddy
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2016
Morton, Penny
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Hicks, Alexander
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Ortiz-Zapater, Elena
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Raghavan, Swetavalli
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Pike, Rosemary
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Noble, Alistair
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Woodfin, Abigail
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Jenkins, Gisli
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Rayner, Emma
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Santis, George
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Parsons, Maddy
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Morton, Penny, Hicks, Alexander, Ortiz-Zapater, Elena, Raghavan, Swetavalli, Pike, Rosemary, Noble, Alistair, Woodfin, Abigail, Jenkins, Gisli, Rayner, Emma, Santis, George and Parsons, Maddy
(2016)
TNFα promotes CAR-dependent migration of leukocytes across epithelial monolayers.
Scientific Reports, 6, [26321].
(doi:10.1038/srep26321).
Abstract
Trans-epithelial migration (TEpM) of leukocytes during inflammation requires engagement with receptors expressed on the basolateral surface of the epithelium. One such receptor is Coxsackie and Adenovirus Receptor (CAR) that binds to Junctional Adhesion Molecule-like (JAM-L) expressed on leukocytes. Here we provide the first evidence that efficient TEpM of monocyte-derived THP-1 cells requires and is controlled by phosphorylation of CAR. We show that TNFα acts in a paracrine manner on epithelial cells via a TNFR1-PI3K-PKCδ pathway leading to CAR phosphorylation and subsequent transmigration across cell junctions. Moreover, we show that CAR is hyper-phosphorylated in vivo in acute and chronic lung inflammation models and this response is required to facilitate immune cell recruitment. This represents a novel mechanism of feedback between leukocytes and epithelial cells during TEpM and may be important in controlling responses to pro-inflammatory cytokines in pathological settings.
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srep26321
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Accepted/In Press date: 3 May 2016
e-pub ahead of print date: 19 May 2016
Published date: 2016
Identifiers
Local EPrints ID: 416601
URI: http://eprints.soton.ac.uk/id/eprint/416601
ISSN: 2045-2322
PURE UUID: 5def0b18-ae51-40d7-9372-7e5e3cd538ca
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Date deposited: 03 Jan 2018 17:30
Last modified: 15 Mar 2024 17:36
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Contributors
Author:
Penny Morton
Author:
Alexander Hicks
Author:
Elena Ortiz-Zapater
Author:
Swetavalli Raghavan
Author:
Rosemary Pike
Author:
Alistair Noble
Author:
Abigail Woodfin
Author:
Gisli Jenkins
Author:
Emma Rayner
Author:
George Santis
Author:
Maddy Parsons
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