TNFα promotes CAR-dependent migration of leukocytes across epithelial monolayers

Penny E. Morton, Alexander Hicks, Elena Ortiz-Zapater, Swetavalli Raghavan, Rosemary Pike, Alistair Noble, Abigail Woodfin, Gisli Jenkins, Emma Rayner, George Santis, Maddy Parsons*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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-PKĆ 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.

Original languageEnglish
Article number26321
JournalScientific Reports
Publication statusPublished - 19 May 2016

Bibliographical note

Funding Information:
This study was funded by the Medical Research Council (MRC) UK, Biotechnology and Biological Sciences Research Council (BBSRC), Royal Society, National Institute for Health Research (NIHR) Clinical Research Facility and NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust, King's College London.


Dive into the research topics of 'TNFα promotes CAR-dependent migration of leukocytes across epithelial monolayers'. Together they form a unique fingerprint.

Cite this