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Progranulin facilitates conversion and function of regulatory T cells under inflammatory conditions.

Wei F, Zhang Y, Zhao W, Yu X, Liu CJ - PLoS ONE (2014)

Bottom Line: PGRN was required for the immunosuppressive function of Tregs, since PGRN-deficient Tregs have a significant decreased ability to suppress the proliferation of effector T cells (Teff).In addition, PGRN deficiency caused a marked reduction in Tregs number in the course of inflammatory arthritis, although no significant difference was observed in the numbers of Tregs between wild type and PGRN deficient mice during development.Furthermore, PGRN deficiency led to significant upregulation of the Wnt receptor gene Fzd2.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, New York University Medical Center, New York, New York, United States of America; Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, China.

ABSTRACT
The progranulin (PGRN) is known to protect regulatory T cells (Tregs) from a negative regulation by TNF-α, and its levels are elevated in various kinds of autoimmune diseases. Whether PGRN directly regulates the conversion of CD4+CD25-T cells into Foxp3-expressing regulatory T cells (iTreg), and whether PGRN affects the immunosuppressive function of Tregs, however, remain unknown. In this study we provide evidences demonstrating that PGRN is able to stimulate the conversion of CD4+CD25-T cells into iTreg in a dose-dependent manner in vitro. In addition, PGRN showed synergistic effects with TGF-β1 on the induction of iTreg. PGRN was required for the immunosuppressive function of Tregs, since PGRN-deficient Tregs have a significant decreased ability to suppress the proliferation of effector T cells (Teff). In addition, PGRN deficiency caused a marked reduction in Tregs number in the course of inflammatory arthritis, although no significant difference was observed in the numbers of Tregs between wild type and PGRN deficient mice during development. Furthermore, PGRN deficiency led to significant upregulation of the Wnt receptor gene Fzd2. Collectively, this study reveals that PGRN directly regulates the numbers and function of Tregs under inflammatory conditions, and provides new insight into the immune regulatory mechanism of PGRN in the pathogenesis of inflammatory and immune-related diseases.

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PGRN treatment does not change the proportions of CD4+CD25+Foxp3+ cells in normal conditions.One week-old Foxp3-RFP reporter mice were divided into two groups, three mice per group. PGRN group mice were treated with 100 µg PGRN every two days for 1 week, and PBS group mice were injected with the same volume of PBS as a control. The lymphocytes of spleen, peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN), and Peyer's patches (PP) were isolated and analyzed by FACS. All data are representative of three independent experiments.
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pone-0112110-g002: PGRN treatment does not change the proportions of CD4+CD25+Foxp3+ cells in normal conditions.One week-old Foxp3-RFP reporter mice were divided into two groups, three mice per group. PGRN group mice were treated with 100 µg PGRN every two days for 1 week, and PBS group mice were injected with the same volume of PBS as a control. The lymphocytes of spleen, peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN), and Peyer's patches (PP) were isolated and analyzed by FACS. All data are representative of three independent experiments.

Mentions: In a separate experiment, one-week-old Foxp3-RFP mice were treated with 100 µg PGRN every two days for 1 week, and the percentage of CD4+RFP+ cells in lymphoid tissues were analyzed by FACS. The results revealed that the numbers of CD4+RFP+ cells in spleen (15.1±0.8% RFP+ cells in PBS group versus 14.0±0.4% in PGRN group), peripheral lymph nodes (16.1±0.2% RFP+ cells in PBS group versus 16.0±0.1% in PGRN group), mesenteric lymph nodes (15.1±1.0%RFP+ cells in PBS group versus 15.9±1.6% in PGRN group), and Peyer's patches (15.3%±2.0 RFP+ cells in PBS group versus 12.3±1.8% in PGRN group) in these two groups was not significantly changed (p>0.05) (Fig. 2). In brief, these findings demonstrate that PGRN treatment does not change the proportions and numbers of CD4+CD25+Foxp3+ cells under physiological conditions.


Progranulin facilitates conversion and function of regulatory T cells under inflammatory conditions.

Wei F, Zhang Y, Zhao W, Yu X, Liu CJ - PLoS ONE (2014)

PGRN treatment does not change the proportions of CD4+CD25+Foxp3+ cells in normal conditions.One week-old Foxp3-RFP reporter mice were divided into two groups, three mice per group. PGRN group mice were treated with 100 µg PGRN every two days for 1 week, and PBS group mice were injected with the same volume of PBS as a control. The lymphocytes of spleen, peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN), and Peyer's patches (PP) were isolated and analyzed by FACS. All data are representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230946&req=5

pone-0112110-g002: PGRN treatment does not change the proportions of CD4+CD25+Foxp3+ cells in normal conditions.One week-old Foxp3-RFP reporter mice were divided into two groups, three mice per group. PGRN group mice were treated with 100 µg PGRN every two days for 1 week, and PBS group mice were injected with the same volume of PBS as a control. The lymphocytes of spleen, peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN), and Peyer's patches (PP) were isolated and analyzed by FACS. All data are representative of three independent experiments.
Mentions: In a separate experiment, one-week-old Foxp3-RFP mice were treated with 100 µg PGRN every two days for 1 week, and the percentage of CD4+RFP+ cells in lymphoid tissues were analyzed by FACS. The results revealed that the numbers of CD4+RFP+ cells in spleen (15.1±0.8% RFP+ cells in PBS group versus 14.0±0.4% in PGRN group), peripheral lymph nodes (16.1±0.2% RFP+ cells in PBS group versus 16.0±0.1% in PGRN group), mesenteric lymph nodes (15.1±1.0%RFP+ cells in PBS group versus 15.9±1.6% in PGRN group), and Peyer's patches (15.3%±2.0 RFP+ cells in PBS group versus 12.3±1.8% in PGRN group) in these two groups was not significantly changed (p>0.05) (Fig. 2). In brief, these findings demonstrate that PGRN treatment does not change the proportions and numbers of CD4+CD25+Foxp3+ cells under physiological conditions.

Bottom Line: PGRN was required for the immunosuppressive function of Tregs, since PGRN-deficient Tregs have a significant decreased ability to suppress the proliferation of effector T cells (Teff).In addition, PGRN deficiency caused a marked reduction in Tregs number in the course of inflammatory arthritis, although no significant difference was observed in the numbers of Tregs between wild type and PGRN deficient mice during development.Furthermore, PGRN deficiency led to significant upregulation of the Wnt receptor gene Fzd2.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, New York University Medical Center, New York, New York, United States of America; Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, China.

ABSTRACT
The progranulin (PGRN) is known to protect regulatory T cells (Tregs) from a negative regulation by TNF-α, and its levels are elevated in various kinds of autoimmune diseases. Whether PGRN directly regulates the conversion of CD4+CD25-T cells into Foxp3-expressing regulatory T cells (iTreg), and whether PGRN affects the immunosuppressive function of Tregs, however, remain unknown. In this study we provide evidences demonstrating that PGRN is able to stimulate the conversion of CD4+CD25-T cells into iTreg in a dose-dependent manner in vitro. In addition, PGRN showed synergistic effects with TGF-β1 on the induction of iTreg. PGRN was required for the immunosuppressive function of Tregs, since PGRN-deficient Tregs have a significant decreased ability to suppress the proliferation of effector T cells (Teff). In addition, PGRN deficiency caused a marked reduction in Tregs number in the course of inflammatory arthritis, although no significant difference was observed in the numbers of Tregs between wild type and PGRN deficient mice during development. Furthermore, PGRN deficiency led to significant upregulation of the Wnt receptor gene Fzd2. Collectively, this study reveals that PGRN directly regulates the numbers and function of Tregs under inflammatory conditions, and provides new insight into the immune regulatory mechanism of PGRN in the pathogenesis of inflammatory and immune-related diseases.

Show MeSH
Related in: MedlinePlus