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


Villegas-Mendez, A; Gwyer Findlay, E; de Souza, JB; Grady, LM; Saris, CJ; Lane, TE; Riley, EM; Couper, KN; (2013) WSX-1 Signalling Inhibits CD4(+) T Cell Migration to the Liver during Malaria Infection by Repressing Chemokine-Independent Pathways. PLoS One, 8 (11). e78486. ISSN 1932-6203 DOI: https://doi.org/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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
PubMed ID: 24244314
Web of Science ID: 327162900019
URI: http://researchonline.lshtm.ac.uk/id/eprint/1366881

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