eCite Digital Repository

Inhibition of CCR6 Function Reduces the Severity of Experimental Autoimmune Encephalomyelitis via Effects on the Priming Phase of the Immune Response

Citation

Liston, A and Kohler, RE and Townley, S and Haylock-Jacobs, S and Comerford, I and Caon, AC and Webster, J and Harrison, JM and Swann, J and Clark-Lewis, I and Korner, H and McColl, SR, Inhibition of CCR6 Function Reduces the Severity of Experimental Autoimmune Encephalomyelitis via Effects on the Priming Phase of the Immune Response, Journal of Immunology, 182, (5) pp. 3121-3130. ISSN 0022-1767 (2009) [Refereed Article]

DOI: doi:10.4049/jimmunol.0713169

Abstract

Chemokines are essential for homeostasis and activation of the immune system. The chemokine ligand/receptor pairing CCL20/CCR6 is interesting because these molecules display characteristics of both homeostatic and activation functions. These dual characteristics suggest a role for CCR6 in the priming and effector phases of the immune response. However, while CCR6 has been implicated in the effector phase in several models, a role in the priming phase is less clear. Herein we analyze the role of CCR6 in these two important arms of the immune response during experimental autoimmune encephalomyelitis (EAE). Both CCR6 and its chemokine ligand CCL20 were up-regulated in the draining lymph nodes and spinal cord during EAE, and CCR6 was up-regulated on CD4+ T cells that had divided following induction of EAE. The functional role of this expression was demonstrated by impaired development of EAE in gene-targeted CCR6-deficient mice and in mice treated either with a neutralizing anti-CCR6 Ab or with a novel receptor antagonist. Inhibition of EAE was due to reduced priming of autoreactive CD4+ T cells probably as a result of impaired late-stage influx of dendritic cells into draining lymph nodes. This was accompanied by reduced egress of activated lymphocytes from the lymph nodes. These results demonstrate a novel role for CCR6 in the mechanism of autoreactive lymphocyte priming and emigration to the efferent lymphatics. Copyright © 2009 by The American Association of Immunologists, Inc.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Korner, H (Professor Heinrich Korner)
ID Code:72560
Year Published:2009
Web of Science® Times Cited:70
Deposited By:Research Division
Deposited On:2011-08-29
Last Modified:2011-08-29
Downloads:0

Repository Staff Only: item control page