Limits...
Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells.

Son YM, Ahn SM, Kim GR, Moon YS, Kim SH, Park YM, Lee WK, Min TS, Han SH, Yun CH - BMC Immunol. (2010)

Bottom Line: Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs.At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s).Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Gwanak-gu, Seoul 151-921, Republic of Korea.

ABSTRACT

Background: Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs) remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs.

Results: Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s). Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF)-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin.

Conclusion: Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.

Show MeSH
TGF-β secreted by CD4+ CD25+ FoxP3+ Tregs, but not by DCs, induces the expansion of Tregs. CD4+ T cells were pre-treated with inhibitor for TGF-β receptor for 1 hr and co-cultured with DCs, followed by resistin treatment for 4 days. Anti-human CD2 and CD3 antibodies were then added to the cells for an additional 3 days. (A) CD25+ FoxP3+ Tregs were measured by flow cytometry. (B) TGF-β production in the supernatant was measured by ELISA. (C) DCs were treated with various concentrations (0, 50, 100, 200 and 500 ng/ml) of resistin for 6 hrs and then TGF-β mRNA expression was measured by RT-PCR. * P< 0.05. The value in each panel indicates the percentage of CD25+ FoxP3+ Tregs. The results represent the mean ± standard deviation from three separate experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2914082&req=5

Figure 4: TGF-β secreted by CD4+ CD25+ FoxP3+ Tregs, but not by DCs, induces the expansion of Tregs. CD4+ T cells were pre-treated with inhibitor for TGF-β receptor for 1 hr and co-cultured with DCs, followed by resistin treatment for 4 days. Anti-human CD2 and CD3 antibodies were then added to the cells for an additional 3 days. (A) CD25+ FoxP3+ Tregs were measured by flow cytometry. (B) TGF-β production in the supernatant was measured by ELISA. (C) DCs were treated with various concentrations (0, 50, 100, 200 and 500 ng/ml) of resistin for 6 hrs and then TGF-β mRNA expression was measured by RT-PCR. * P< 0.05. The value in each panel indicates the percentage of CD25+ FoxP3+ Tregs. The results represent the mean ± standard deviation from three separate experiments.

Mentions: To investigate whether TGF-β secreted from DCs is involved in the induction of Tregs, CD4+ T cells were pre-treated with TGF-β receptor inhibitor, co-cultured with DCs, and concomitantly treated with resistin. Tregs were induced when the cells were treated with resistin as expected, but treatment with TGF-β receptor inhibitor suppressed such induction (figure 4A). We also examined the level of TGF-β in the culture supernatant. TGF-β increased in CD4+ T cells when co-cultured with DCs and treated with resistin (figure 4B). The expression of TGF-β mRNA was not significantly different in DCs alone treated with resistin (figure 4C). These results suggest that TGF-β produced from CD4+ T cells co-cultured with DCs together with resistin treatment, was the major source to induce the differentiation of Tregs, rather than TGF-β secreted from DCs.


Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells.

Son YM, Ahn SM, Kim GR, Moon YS, Kim SH, Park YM, Lee WK, Min TS, Han SH, Yun CH - BMC Immunol. (2010)

TGF-β secreted by CD4+ CD25+ FoxP3+ Tregs, but not by DCs, induces the expansion of Tregs. CD4+ T cells were pre-treated with inhibitor for TGF-β receptor for 1 hr and co-cultured with DCs, followed by resistin treatment for 4 days. Anti-human CD2 and CD3 antibodies were then added to the cells for an additional 3 days. (A) CD25+ FoxP3+ Tregs were measured by flow cytometry. (B) TGF-β production in the supernatant was measured by ELISA. (C) DCs were treated with various concentrations (0, 50, 100, 200 and 500 ng/ml) of resistin for 6 hrs and then TGF-β mRNA expression was measured by RT-PCR. * P< 0.05. The value in each panel indicates the percentage of CD25+ FoxP3+ Tregs. The results represent the mean ± standard deviation from three separate experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2914082&req=5

Figure 4: TGF-β secreted by CD4+ CD25+ FoxP3+ Tregs, but not by DCs, induces the expansion of Tregs. CD4+ T cells were pre-treated with inhibitor for TGF-β receptor for 1 hr and co-cultured with DCs, followed by resistin treatment for 4 days. Anti-human CD2 and CD3 antibodies were then added to the cells for an additional 3 days. (A) CD25+ FoxP3+ Tregs were measured by flow cytometry. (B) TGF-β production in the supernatant was measured by ELISA. (C) DCs were treated with various concentrations (0, 50, 100, 200 and 500 ng/ml) of resistin for 6 hrs and then TGF-β mRNA expression was measured by RT-PCR. * P< 0.05. The value in each panel indicates the percentage of CD25+ FoxP3+ Tregs. The results represent the mean ± standard deviation from three separate experiments.
Mentions: To investigate whether TGF-β secreted from DCs is involved in the induction of Tregs, CD4+ T cells were pre-treated with TGF-β receptor inhibitor, co-cultured with DCs, and concomitantly treated with resistin. Tregs were induced when the cells were treated with resistin as expected, but treatment with TGF-β receptor inhibitor suppressed such induction (figure 4A). We also examined the level of TGF-β in the culture supernatant. TGF-β increased in CD4+ T cells when co-cultured with DCs and treated with resistin (figure 4B). The expression of TGF-β mRNA was not significantly different in DCs alone treated with resistin (figure 4C). These results suggest that TGF-β produced from CD4+ T cells co-cultured with DCs together with resistin treatment, was the major source to induce the differentiation of Tregs, rather than TGF-β secreted from DCs.

Bottom Line: Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs.At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s).Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Gwanak-gu, Seoul 151-921, Republic of Korea.

ABSTRACT

Background: Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs) remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs.

Results: Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s). Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF)-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin.

Conclusion: Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.

Show MeSH