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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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IL-27 induces the expression of IL-10 and IFN-γ in CD56bright and CD56dim NK cells.IL-27 decreases the proliferation of NK cells subsets and enhances their survival. (a) and (b) Expression of IL-10 and IFN-γ as measured by real-time PCR. Purified CD56bright and CD56dim NK cells were cultured for 24 hours in medium only, in presence of IL-27 only or in presence IL-12 plus IL-15 with or without IL-27. (c) Proliferation of CD56bright and CD56dim NK cells after culture in medium only, with IL-27 only and with IL-12 plus IL-15 with or without IL-27. Cell proliferation is shown as mean c.p.m.+s.d. in triplicate wells. (d) Viability of CD56bright and CD56dim NK cells as determined by the FACS after 72 hours of culture in the presence of the IL-27 compared to no stimulus, and in the presence of IL-12 plus IL-15 with or without IL-27. Dead cells were selected as AAD-positive cells. One experiment of 5–10 independent experiments is shown in each panel.
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pone-0026173-g002: IL-27 induces the expression of IL-10 and IFN-γ in CD56bright and CD56dim NK cells.IL-27 decreases the proliferation of NK cells subsets and enhances their survival. (a) and (b) Expression of IL-10 and IFN-γ as measured by real-time PCR. Purified CD56bright and CD56dim NK cells were cultured for 24 hours in medium only, in presence of IL-27 only or in presence IL-12 plus IL-15 with or without IL-27. (c) Proliferation of CD56bright and CD56dim NK cells after culture in medium only, with IL-27 only and with IL-12 plus IL-15 with or without IL-27. Cell proliferation is shown as mean c.p.m.+s.d. in triplicate wells. (d) Viability of CD56bright and CD56dim NK cells as determined by the FACS after 72 hours of culture in the presence of the IL-27 compared to no stimulus, and in the presence of IL-12 plus IL-15 with or without IL-27. Dead cells were selected as AAD-positive cells. One experiment of 5–10 independent experiments is shown in each panel.

Mentions: An important way by which NK cells, and especially the CD56bright subset, influence innate and adaptive immune responses is the secretion of cytokines, among them IFN-γ is the most prominent, and under certain conditions, IL-10 is secreted [16] [3]. We asked whether the reported effect of IL-27 on IFN-γ secretion by NK cells occurred in both subsets, and whether IL-27 could also induce IL-10 secretion in NK cell subsets, given that this is observed following IL-27 stimulation of CD4+ T cells. We measured the expression of IFN-γ and IL-10 by real-time PCR. Although we did not observe induction of these cytokines when we stimulated NK cells with IL-27 alone (figure 2a and figure 2b) we observed increased expression of both IL-10 and IFN-γ in CD56bright and CD56dim NK cells stimulated with IL-12 and IL-15 and treated with IL-27 (figure 2a and 2b). It is known that IL-12 and IL-15 induce the secretion of both cytokines in NK cells [3]. The induction of a “pro-inflammatory” cytokine, such as IFN-γ, and of the immunosuppressive cytokine IL-10, may appear contradictory. However, it has been shown that in NK cells, IL-10 secretion may occur in association with IFN-γ and that IL-10+IFN-γ+ NK cells have immunosuppressive properties e.g., suppressing the secretion of the pro-inflammatory cytokine IL-12 by dendritic cells [17]. Of note regulatory Tr1 cells, induced by IL-27, also produce both IL-10 and IFN-γ [10].


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

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

IL-27 induces the expression of IL-10 and IFN-γ in CD56bright and CD56dim NK cells.IL-27 decreases the proliferation of NK cells subsets and enhances their survival. (a) and (b) Expression of IL-10 and IFN-γ as measured by real-time PCR. Purified CD56bright and CD56dim NK cells were cultured for 24 hours in medium only, in presence of IL-27 only or in presence IL-12 plus IL-15 with or without IL-27. (c) Proliferation of CD56bright and CD56dim NK cells after culture in medium only, with IL-27 only and with IL-12 plus IL-15 with or without IL-27. Cell proliferation is shown as mean c.p.m.+s.d. in triplicate wells. (d) Viability of CD56bright and CD56dim NK cells as determined by the FACS after 72 hours of culture in the presence of the IL-27 compared to no stimulus, and in the presence of IL-12 plus IL-15 with or without IL-27. Dead cells were selected as AAD-positive cells. One experiment of 5–10 independent experiments is shown in each panel.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3198386&req=5

pone-0026173-g002: IL-27 induces the expression of IL-10 and IFN-γ in CD56bright and CD56dim NK cells.IL-27 decreases the proliferation of NK cells subsets and enhances their survival. (a) and (b) Expression of IL-10 and IFN-γ as measured by real-time PCR. Purified CD56bright and CD56dim NK cells were cultured for 24 hours in medium only, in presence of IL-27 only or in presence IL-12 plus IL-15 with or without IL-27. (c) Proliferation of CD56bright and CD56dim NK cells after culture in medium only, with IL-27 only and with IL-12 plus IL-15 with or without IL-27. Cell proliferation is shown as mean c.p.m.+s.d. in triplicate wells. (d) Viability of CD56bright and CD56dim NK cells as determined by the FACS after 72 hours of culture in the presence of the IL-27 compared to no stimulus, and in the presence of IL-12 plus IL-15 with or without IL-27. Dead cells were selected as AAD-positive cells. One experiment of 5–10 independent experiments is shown in each panel.
Mentions: An important way by which NK cells, and especially the CD56bright subset, influence innate and adaptive immune responses is the secretion of cytokines, among them IFN-γ is the most prominent, and under certain conditions, IL-10 is secreted [16] [3]. We asked whether the reported effect of IL-27 on IFN-γ secretion by NK cells occurred in both subsets, and whether IL-27 could also induce IL-10 secretion in NK cell subsets, given that this is observed following IL-27 stimulation of CD4+ T cells. We measured the expression of IFN-γ and IL-10 by real-time PCR. Although we did not observe induction of these cytokines when we stimulated NK cells with IL-27 alone (figure 2a and figure 2b) we observed increased expression of both IL-10 and IFN-γ in CD56bright and CD56dim NK cells stimulated with IL-12 and IL-15 and treated with IL-27 (figure 2a and 2b). It is known that IL-12 and IL-15 induce the secretion of both cytokines in NK cells [3]. The induction of a “pro-inflammatory” cytokine, such as IFN-γ, and of the immunosuppressive cytokine IL-10, may appear contradictory. However, it has been shown that in NK cells, IL-10 secretion may occur in association with IFN-γ and that IL-10+IFN-γ+ NK cells have immunosuppressive properties e.g., suppressing the secretion of the pro-inflammatory cytokine IL-12 by dendritic cells [17]. Of note regulatory Tr1 cells, induced by IL-27, also produce both IL-10 and IFN-γ [10].

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