Posttranscriptional regulation of Il10 gene expression allows natural killer cells to express immunoregulatory function

TY - JOUR

T1 - Posttranscriptional regulation of Il10 gene expression allows natural killer cells to express immunoregulatory function

AU - Maroof, Asher

AU - Beattie, Lynette

AU - Zubairi, Soombul

AU - Svensson, Mattias

AU - Stager, Simona

AU - Kaye, Paul M.

PY - 2008/8/15

Y1 - 2008/8/15

N2 - 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.

AB - 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.

KW - EXPERIMENTAL VISCERAL LEISHMANIASIS

KW - CD4(+) T-CELLS

KW - HUMAN NK CELLS

KW - DENDRITIC CELLS

KW - AUTOIMMUNE-DISEASE

KW - IL-10 PRODUCTION

KW - IN-SITU

KW - INFECTION

KW - ACTIVATION

KW - RESPONSES

UR - http://www.scopus.com/inward/record.url?scp=48749130944&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2008.06.012

DO - 10.1016/j.immuni.2008.06.012

M3 - Article

C2 - 18701085

SN - 1074-7613

VL - 29

SP - 295

EP - 305

JO - Immunity

JF - Immunity

IS - 2

ER -