Villegas-Mendez, A;
Gwyer Findlay, E;
de Souza, JB;
Grady, L-M;
Saris, CJ;
Lane, TE;
Riley, EM;
(2013)
WSX-1 Signalling Inhibits CD4+ T Cell Migration to the Liver during Malaria Infection by Repressing Chemokine-Independent Pathways.
PLoS ONE
, 8
(11)
, Article e78486. 10.1371/journal.pone.0078486.
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Abstract
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(+) T cells in the liver of infected IL27R(-/-) (WSX-1(-/-)) 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(+) T cells towards infection-derived liver cells, but also suppresses the production of soluble liver-derived mediator(s) that direct CD4(+) T cell movement towards the inflamed tissue. Although CCL4 and CCL5 expression was higher in livers of infected WSX-1(-/-) mice than infected WT mice, and hepatic CD4(+) T cells from WSX-1(-/-) mice expressed higher levels of CCR5 than cells from WT mice, migration of CD4(+) T cells to the liver of WSX-1(-/-) mice during infection was not controlled by chemokine (R) signalling. However, anti-IL-12p40 treatment reduced migration of CD4(+) 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(+) 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.
| Type: | Article |
|---|---|
| Title: | WSX-1 Signalling Inhibits CD4+ T Cell Migration to the Liver during Malaria Infection by Repressing Chemokine-Independent Pathways |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0078486 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0078486 |
| Language: | English |
| Additional information: | © 2013 Villegas-Mendez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1416466 |
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