Imperial College London

DrJamesPease

Faculty of MedicineNational Heart & Lung Institute

Reader in Leukocyte Biology
 
 
 
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Contact

 

+44 (0)20 7594 3162j.pease Website

 
 
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Location

 

109Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Anderson:2020:10.1002/JLB.2A0120-089RR,
author = {Anderson, C and Patel, P and Viney, J and Phillips, R and Solari, R and Pease, J},
doi = {10.1002/JLB.2A0120-089RR},
journal = {Journal of Leukocyte Biology},
pages = {455--466},
title = {A degradatory fate for CCR4 suggests a primary role in Th2 inflammation},
url = {http://dx.doi.org/10.1002/JLB.2A0120-089RR},
volume = {107},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - CCR4 is the sole receptor for the chemokines CCL22 and CCL17. Clinical studies of asthmatic airways have shown levels of both ligands and CCR4+ Th2 cells to be elevated, suggestive of a role in disease. Consequently, CCR4 has aroused much interest as a potential therapeutic target and an understanding of how its cell surface expression is regulated is highly desirable. To this end, receptor expression, receptor endocytosis, and chemotaxis were assessed using transfectants expressing CCR4, CCR4+ human T cell lines, and human Th2 cells polarized in vitro. CCL17 and CCL22 drove rapid endocytosis of CCR4 in a dosedependent manner. Replenishment at the cell surface was slow and sensitive to cycloheximide, suggestive of de novo synthesis of CCR4. Constitutive CCR4 endocytosis was also observed, with the internalized CCR4 found to be significantly degraded over a 6h incubation. Truncation of the CCR4 Cterminus by 40 amino acids had no effect on cell surface expression, but resulted in significant impairment of ligandinduced endocytosis. Consequently, migration to both CCL17 and CCL22 was significantly enhanced. In contrast, truncation of CCR4 did not impair constitutive endocytosis or degradation, suggesting the use of alternative receptor motifs in these processes. We conclude that CCR4 cell surface levels are tightly regulated, with a degradative fate for endocytosed receptor. We postulate that this strict control is desirable, given that Th2 cells recruited by CCR4 can induce the further expression of CCR4 ligands in a positive feedback loop, thereby enhancing allergic inflammation.
AU - Anderson,C
AU - Patel,P
AU - Viney,J
AU - Phillips,R
AU - Solari,R
AU - Pease,J
DO - 10.1002/JLB.2A0120-089RR
EP - 466
PY - 2020///
SN - 0741-5400
SP - 455
TI - A degradatory fate for CCR4 suggests a primary role in Th2 inflammation
T2 - Journal of Leukocyte Biology
UR - http://dx.doi.org/10.1002/JLB.2A0120-089RR
UR - http://hdl.handle.net/10044/1/76885
VL - 107
ER -