WSX-1 Signalling Inhibits CD4.sup.+ T Cell Migration to the Liver during Malaria Infection by Repressing Chemokine-Independent Pathways

IL-27 is an important and non-redundant regulator of effector T cell accumulation in non-lymphoid tissues during infection. Using malaria as a model systemic pro-inflammatory infection, we demonstrate that the aberrant accumulation of CD4.sup.+ T cells in the liver of infected IL27R.sup.-/- (WSX-1.s...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e78486
Main Authors: Villegas-Mendez, Ana, Gwyer Findlay, Emily, de Souza, J. Brian, Grady, Lisa-Marie, Saris, Christiaan J, Lane, Thomas E, Riley, Eleanor M, Couper, Kevin N
Format: Article
Language:English
Subjects:
Analysis
Cell death
Health aspects
Infection
Liver
Malaria
T cells
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Summary:IL-27 is an important and non-redundant regulator of effector T cell accumulation in non-lymphoid tissues during infection. Using malaria as a model systemic pro-inflammatory infection, we demonstrate that the aberrant accumulation of CD4.sup.+ T cells in the liver of infected IL27R.sup.-/- (WSX-1.sup.-/-) mice is a result of differences in cellular recruitment, rather than changes in T cell proliferation or cell death. We show that IL-27 both inhibits the migratory capacity of infection-derived CD4.sup.+ T cells towards infection-derived liver cells, but also suppresses the production of soluble liver-derived mediator(s) that direct CD4.sup.+ T cell movement towards the inflamed tissue. Although CCL4 and CCL5 expression was higher in livers of infected WSX-1.sup.-/- mice than infected WT mice, and hepatic CD4.sup.+ T cells from WSX-1.sup.-/- mice expressed higher levels of CCR5 than cells from WT mice, migration of CD4.sup.+ T cells to the liver of WSX-1.sup.-/- mice during infection was not controlled by chemokine (R) signalling. However, anti-IL-12p40 treatment reduced migration of CD4.sup.+ T cells towards infection-derived liver cells, primarily by abrogating the hepatotropic migratory capacity of T cells, rather than diminishing soluble tissue-derived migratory signals. These results indicate that IL-27R signalling restricts CD4.sup.+ T cell accumulation within the liver during infection primarily by suppressing T cell chemotaxis, which may be linked to its capacity to repress Th1 differentiation, as well as by inhibiting the production of soluble, tissue-derived chemotaxins.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0078486