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PMID: 18701085 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Posttranscriptional regulation of II10 gene expression allows natural killer cells to express immunoregulatory function.

Immunity ·Vol. 29 ·No. 2 ·2008-08-15 ·Pages 295-305

Maroof A, Beattie L, Zubairi S, Svensson M, Stager S, Kaye PM

Abstract

Natural killer (NK) cells play a well-recognized role in early pathogen containment and in shaping acquired cell-mediated immunity. However, indirect evidence in humans and experimental models has suggested that NK cells also play negative regulatory roles during chronic disease. To formally test this hypothesis, we employed a well-defined experimental model of visceral leishmaniasis. Our data demonstrated that NKp46(+)CD49b(+)CD3(-) NK cells were recruited to the spleen and into hepatic granulomas, where they inhibited host protective immunity in an interleukin-10 (IL-10)-dependent manner. Although IL-10 mRNA could be detected in activated NK cells 24 hr after infection, the inhibitory function of NK cells was only acquired later during infection, coincident with increased IL-10 mRNA stability and an enhanced capacity to secrete IL-10 protein. Our data support a growing body of literature that implicates NK cells as negative regulators of cell-mediated immunity and suggest that NK cells, like CD4(+) T helper 1 cells, may acquire immunoregulatory functions as a consequence of extensive activation.

MeSH Terms
Animals CD4-Positive T-Lymphocytes/immunology Gene Expression Granuloma/immunology,metabolism Interleukin-10/genetics,immunology,metabolism Killer Cells, Natural/cytology,immunology,metabolism Leishmania donovani/immunology Leishmaniasis, Visceral/immunology,parasitology Liver/immunology Macrophages/immunology,metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL RNA, Messenger/genetics,metabolism
Chemicals
RNA, Messenger Interleukin-10
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Maroof Asher
Immunology and Infection Unit, Hull York Medical School and Department of Biology, University of York, Wentworth Way, York YO10 5YW, UK.
Beattie Lynette
Zubairi Soombul
Svensson Mattias
Stager Simona
Kaye Paul M
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2008.06.012
Published
2008-08-15
Pages
295-305
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2656759
Subset
IM
Grants
Wellcome Trust · United Kingdom
Wellcome Trust · 065308 · United Kingdom
Medical Research Council · G0400786 · United Kingdom
Medical Research Council · G0400786(71636) · United Kingdom
External Links
PubMed source DOI: 10.1016/j.immuni.2008.06.012 PMC Full Text View journal details
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