Pepro Tech
Originally published online as doi:10.1189/jlb.0408234 on June 27, 2008

Published online before print June 27, 2008
This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
jlb.0408234v1
84/4/1202    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Webb, A.
Right arrow Articles by Jopling, L. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Webb, A.
Right arrow Articles by Jopling, L. A.
(Journal of Leukocyte Biology. 2008;84:1202-1212.)
© 2008 by Society for Leukocyte Biology

Evidence for PI-3K-dependent migration of Th17-polarized cells in response to CCR2 and CCR6 agonists

Adam Webb*,1, Andrew Johnson{dagger},1,2, Mara Fortunato{dagger}, Adam Platt{dagger}, Tom Crabbe{ddagger}, Mark I. Christie{dagger}, Gillian F. Watt{dagger}, Stephen G. Ward*,3 and Louise A. Jopling{dagger}

* Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom;
{dagger} UCB, Granta Park, Great Abington, Cambridge, United Kingdom; and
{ddagger} UCB, Slough, United Kingdom

3 Correspondence: Inflammatory Cell Biology Lab, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. E-mail: S.G.Ward{at}bath.ac.uk

IL-17-producing Th cells (Th17) are a distinct subset of effector cells that bridge the innate and adaptive immune system and are implicated in autoimmune disease processes. CD4+ splenocytes from DO11.10 mice were activated with OVA peptide323–339 and maintained under Th17 polarization conditions, resulting in significantly higher proportions of IL-17+ T cells compared with nonpolarized (Th0) cells. Th17-polarizing conditions significantly increased the proportion of cells expressing the chemokine receptors CCR2, CCR6, and CCR9 when compared with Th0 cells. In contrast, there was a significant decrease in the proportion of cells expressing CXCR3 under Th17-polarizing conditions compared with nonpolarizing conditions. The respective chemokine agonists for CCR2 (CCL2 and CCL12), CCR6 (CCL20), and CCR9 (CCL25) elicited migration and PI-3K-dependent signaling events in Th17-polarized cells, thus indicating that all three receptors were functionally and biochemically responsive. Furthermore, postmigration phenotypic analysis demonstrated that the agonists for CCR2 and CCR6, but not CCR9, stimulated a modest enrichment of IL-17+ cells compared with the premigration population. Pan-isoform inhibitors of PI-3K/Akt signaling prevented CCR2- and CCR6-mediated, polarized Th17 cell migration in a concentration-dependent manner. The unique chemokine receptor expression pattern of Th17 cells and their corresponding PI-3K-dependent migratory responses are important for understanding the pathogenesis of autoimmune diseases and may provide opportunities for the application of CCR2 and CCR6 antagonists and PI-3K isoform-selective inhibitors in defined inflammatory settings.

Key Words: T cells • chemokines • cell trafficking • inflammation • signal transduction




This article has been cited by other articles:


Home page
 BloodHome page
M. Pelletier, L. Maggi, A. Micheletti, E. Lazzeri, N. Tamassia, C. Costantini, L. Cosmi, C. Lunardi, F. Annunziato, S. Romagnani, et al.
Evidence for a cross-talk between human neutrophils and Th17 cells
Blood, January 14, 2010; 115(2): 335 - 343.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
A. Mildner, M. Mack, H. Schmidt, W. Bruck, M. Djukic, M. D. Zabel, A. Hille, J. Priller, and M. Prinz
CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system
Brain, September 1, 2009; 132(9): 2487 - 2500.
[Abstract] [Full Text] [PDF]