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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

IL-27 does not induce cytotoxicity in CD56dim NK cells, but imparts immunoregulatory function to CD56bright NK cells.Degranulation (a) and cytotoxicity (b) of CD56dim NK cells after stimulation with or without IL-27. Purified CD56dim NKcells were cultured for 72 hours in the presence or absence of IL-27. Viable cells were re-sorted and cultured with or without the target cell line K562 for 4 hours or were stained for CD107a. One representative experiment is shown of 5–7 experiments. (c) Suppression assay of CD56bright NK cells activated for 72 hours with IL-27. Live cells were sorted and cultured with autologous purified CD4+ T cells in the presence of anti-CD3 and anti-CD28 coated beads. Cell proliferation was assessed after five days as shown with mean+s.d. in triplicate wells, one of seven experiments is shown. (d) Suppressive activity of NK cells activated in the presence of IL-27 and incubated in contact with responder T cells (Control) or with a transwell (Transwell). (e) Expression of molecules involved in NK cell mediated cytotoxicity in CD56bright NK cells treated with IL-27 after 72 hours.
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pone-0026173-g003: IL-27 does not induce cytotoxicity in CD56dim NK cells, but imparts immunoregulatory function to CD56bright NK cells.Degranulation (a) and cytotoxicity (b) of CD56dim NK cells after stimulation with or without IL-27. Purified CD56dim NKcells were cultured for 72 hours in the presence or absence of IL-27. Viable cells were re-sorted and cultured with or without the target cell line K562 for 4 hours or were stained for CD107a. One representative experiment is shown of 5–7 experiments. (c) Suppression assay of CD56bright NK cells activated for 72 hours with IL-27. Live cells were sorted and cultured with autologous purified CD4+ T cells in the presence of anti-CD3 and anti-CD28 coated beads. Cell proliferation was assessed after five days as shown with mean+s.d. in triplicate wells, one of seven experiments is shown. (d) Suppressive activity of NK cells activated in the presence of IL-27 and incubated in contact with responder T cells (Control) or with a transwell (Transwell). (e) Expression of molecules involved in NK cell mediated cytotoxicity in CD56bright NK cells treated with IL-27 after 72 hours.

Mentions: Cytotoxicity is an important function of CD56dim NK cells [22]. Resting CD56dim NK cells are poorly cytotoxic, while activation with cytokines such as IL-2, IL-12, IL-15 and IL-21 enhances their cytotoxic features [20]. Thus, we tested IL-27-stimulated CD56dim NK cells in a cytotoxic assay using K562 cells and measured both the percentage of dead cells and the percentage of degranulated (CD107a positive) CD56dim NK cells as a marker for cytotoxicity. IL-27 stimulation did not enhance cytotoxicity by CD56dim NK cells or influenced the degranulation as measured by CD107a expression (figure 3a and 3b).


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

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

IL-27 does not induce cytotoxicity in CD56dim NK cells, but imparts immunoregulatory function to CD56bright NK cells.Degranulation (a) and cytotoxicity (b) of CD56dim NK cells after stimulation with or without IL-27. Purified CD56dim NKcells were cultured for 72 hours in the presence or absence of IL-27. Viable cells were re-sorted and cultured with or without the target cell line K562 for 4 hours or were stained for CD107a. One representative experiment is shown of 5–7 experiments. (c) Suppression assay of CD56bright NK cells activated for 72 hours with IL-27. Live cells were sorted and cultured with autologous purified CD4+ T cells in the presence of anti-CD3 and anti-CD28 coated beads. Cell proliferation was assessed after five days as shown with mean+s.d. in triplicate wells, one of seven experiments is shown. (d) Suppressive activity of NK cells activated in the presence of IL-27 and incubated in contact with responder T cells (Control) or with a transwell (Transwell). (e) Expression of molecules involved in NK cell mediated cytotoxicity in CD56bright NK cells treated with IL-27 after 72 hours.
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Related In: Results  -  Collection

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

pone-0026173-g003: IL-27 does not induce cytotoxicity in CD56dim NK cells, but imparts immunoregulatory function to CD56bright NK cells.Degranulation (a) and cytotoxicity (b) of CD56dim NK cells after stimulation with or without IL-27. Purified CD56dim NKcells were cultured for 72 hours in the presence or absence of IL-27. Viable cells were re-sorted and cultured with or without the target cell line K562 for 4 hours or were stained for CD107a. One representative experiment is shown of 5–7 experiments. (c) Suppression assay of CD56bright NK cells activated for 72 hours with IL-27. Live cells were sorted and cultured with autologous purified CD4+ T cells in the presence of anti-CD3 and anti-CD28 coated beads. Cell proliferation was assessed after five days as shown with mean+s.d. in triplicate wells, one of seven experiments is shown. (d) Suppressive activity of NK cells activated in the presence of IL-27 and incubated in contact with responder T cells (Control) or with a transwell (Transwell). (e) Expression of molecules involved in NK cell mediated cytotoxicity in CD56bright NK cells treated with IL-27 after 72 hours.
Mentions: Cytotoxicity is an important function of CD56dim NK cells [22]. Resting CD56dim NK cells are poorly cytotoxic, while activation with cytokines such as IL-2, IL-12, IL-15 and IL-21 enhances their cytotoxic features [20]. Thus, we tested IL-27-stimulated CD56dim NK cells in a cytotoxic assay using K562 cells and measured both the percentage of dead cells and the percentage of degranulated (CD107a positive) CD56dim NK cells as a marker for cytotoxicity. IL-27 stimulation did not enhance cytotoxicity by CD56dim NK cells or influenced the degranulation as measured by CD107a expression (figure 3a and 3b).

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