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IL-27 imparts immunoregulatory function to human NK cell subsets.

Laroni A, Gandhi R, Beynon V, Weiner HL - PLoS ONE (2011)

Bottom Line: We found that IL-27 treatment results in increased IL-10 and IFN-γ expression, increased viability and decreased proliferation in both CD56(bright) and CD56(dim) NK cell subsets.More importantly, IL-27 treatment imparts regulatory activity to CD56(bright) NK cells, which mediates its suppressive function on T cells in a contact-dependent manner.There is growing evidence that CD56(bright) NK cell-mediated immunoregulation plays an important role in the control of autoimmunity.

View Article: PubMed Central - PubMed

Affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
Interleukin-27 (IL-27) is a cytokine with multiple roles in regulating the immune response, but its effect on human CD56(bright) and CD56(dim) NK cell subsets is unknown. NK cell subsets interact with other components of the immune system, leading to cytotoxicity or immunoregulation depending on stimulating factors. We found that IL-27 treatment results in increased IL-10 and IFN-γ expression, increased viability and decreased proliferation in both CD56(bright) and CD56(dim) NK cell subsets. More importantly, IL-27 treatment imparts regulatory activity to CD56(bright) NK cells, which mediates its suppressive function on T cells in a contact-dependent manner. There is growing evidence that CD56(bright) NK cell-mediated immunoregulation plays an important role in the control of autoimmunity. Thus, understanding the role of IL-27 in NK cell function has important implications for treatment of autoimmune disorders.

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Related in: MedlinePlus

NK cells express IL-27 receptor.(a) Expression of WSX-1, subunit of IL-27R, as measured by real-time PCR in purified the CD56bright and CD56dim NK cells. Mean ± standard deviation of a representative experiment (of three independent experiments) is shown. (b) Expression of IL-27 receptor subunit WSX-1 on the surface of purified CD56bright and CD56dim NK cells, as measured by the FACS. One representative experiment of eight experiments. (c) FACS histogram showing expression of IL-27R (red profiles) on CD56bright and (d) on CD56dim NK cells compared to isotype control (filled grey profiles).
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pone-0026173-g001: NK cells express IL-27 receptor.(a) Expression of WSX-1, subunit of IL-27R, as measured by real-time PCR in purified the CD56bright and CD56dim NK cells. Mean ± standard deviation of a representative experiment (of three independent experiments) is shown. (b) Expression of IL-27 receptor subunit WSX-1 on the surface of purified CD56bright and CD56dim NK cells, as measured by the FACS. One representative experiment of eight experiments. (c) FACS histogram showing expression of IL-27R (red profiles) on CD56bright and (d) on CD56dim NK cells compared to isotype control (filled grey profiles).

Mentions: IL27R is comprised of two polypeptide chains, IL-27RA (WSX1) and gp130: of them, WSX1 is specific for IL-27, whereas gp130 is shared by various cytokine receptor complexes [13]. Although the expression of IL-27R on activated and non-activated NK cells has been shown previously, it was never analyzed in different subsets of NK cells, which display remarkable differences in phenotype, including receptors for cytokines [15]. Thus, the expression of IL-27R on human NK cells subsets was determined by real time PCR and by FACS analysis of surface expression of WSX1 specific subunit on both NK subsets. We found that both subsets express mRNA for IL27R (figure 1a) and express the protein on the surface with an increased expression on surface of CD56bright compared to CD56dim subset (p<0.05, figure 1b and figure 1c) as shown by FACS analysis.


IL-27 imparts immunoregulatory function to human NK cell subsets.

Laroni A, Gandhi R, Beynon V, Weiner HL - PLoS ONE (2011)

NK cells express IL-27 receptor.(a) Expression of WSX-1, subunit of IL-27R, as measured by real-time PCR in purified the CD56bright and CD56dim NK cells. Mean ± standard deviation of a representative experiment (of three independent experiments) is shown. (b) Expression of IL-27 receptor subunit WSX-1 on the surface of purified CD56bright and CD56dim NK cells, as measured by the FACS. One representative experiment of eight experiments. (c) FACS histogram showing expression of IL-27R (red profiles) on CD56bright and (d) on CD56dim NK cells compared to isotype control (filled grey profiles).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198386&req=5

pone-0026173-g001: NK cells express IL-27 receptor.(a) Expression of WSX-1, subunit of IL-27R, as measured by real-time PCR in purified the CD56bright and CD56dim NK cells. Mean ± standard deviation of a representative experiment (of three independent experiments) is shown. (b) Expression of IL-27 receptor subunit WSX-1 on the surface of purified CD56bright and CD56dim NK cells, as measured by the FACS. One representative experiment of eight experiments. (c) FACS histogram showing expression of IL-27R (red profiles) on CD56bright and (d) on CD56dim NK cells compared to isotype control (filled grey profiles).
Mentions: IL27R is comprised of two polypeptide chains, IL-27RA (WSX1) and gp130: of them, WSX1 is specific for IL-27, whereas gp130 is shared by various cytokine receptor complexes [13]. Although the expression of IL-27R on activated and non-activated NK cells has been shown previously, it was never analyzed in different subsets of NK cells, which display remarkable differences in phenotype, including receptors for cytokines [15]. Thus, the expression of IL-27R on human NK cells subsets was determined by real time PCR and by FACS analysis of surface expression of WSX1 specific subunit on both NK subsets. We found that both subsets express mRNA for IL27R (figure 1a) and express the protein on the surface with an increased expression on surface of CD56bright compared to CD56dim subset (p<0.05, figure 1b and figure 1c) as shown by FACS analysis.

Bottom Line: We found that IL-27 treatment results in increased IL-10 and IFN-γ expression, increased viability and decreased proliferation in both CD56(bright) and CD56(dim) NK cell subsets.More importantly, IL-27 treatment imparts regulatory activity to CD56(bright) NK cells, which mediates its suppressive function on T cells in a contact-dependent manner.There is growing evidence that CD56(bright) NK cell-mediated immunoregulation plays an important role in the control of autoimmunity.

View Article: PubMed Central - PubMed

Affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
Interleukin-27 (IL-27) is a cytokine with multiple roles in regulating the immune response, but its effect on human CD56(bright) and CD56(dim) NK cell subsets is unknown. NK cell subsets interact with other components of the immune system, leading to cytotoxicity or immunoregulation depending on stimulating factors. We found that IL-27 treatment results in increased IL-10 and IFN-γ expression, increased viability and decreased proliferation in both CD56(bright) and CD56(dim) NK cell subsets. More importantly, IL-27 treatment imparts regulatory activity to CD56(bright) NK cells, which mediates its suppressive function on T cells in a contact-dependent manner. There is growing evidence that CD56(bright) NK cell-mediated immunoregulation plays an important role in the control of autoimmunity. Thus, understanding the role of IL-27 in NK cell function has important implications for treatment of autoimmune disorders.

Show MeSH
Related in: MedlinePlus