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Myelin-specific T helper 17 cells promote adult hippocampal neurogenesis through indirect mechanisms.

Niebling J, E Rünker A, Schallenberg S, Kretschmer K, Kempermann G - F1000Res (2014)

Bottom Line: CD4 (+) T cells provide a neuro-immunological link in the regulation of adult hippocampal neurogenesis, but the exact mechanisms underlying enhanced neural precursor cell proliferation and the relative contribution of different T helper (Th) cell subsets have remained unclear.We found that base-line proliferation of hippocampal precursor cells in a T cell-deficient mouse model of impaired hippocampal neurogenesis can be restored upon adoptive transfer with homogeneous Th17 populations enriched for myelin-reactive T cell receptors.In these experiments, enhanced proliferation was independent of direct interactions of infiltrating Th17 cells with precursor cells or neighboring cells in the hippocampal neurogenic niche.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Immunology/Immune Regulation, CRTD - Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany ; Genomics of Regeneration, CRTD - Center for Regenerative Therapies Dresden, Technische Universität Dresden, , Fetscherstraße 105, 01307 Dresden, Germany.

ABSTRACT
CD4 (+) T cells provide a neuro-immunological link in the regulation of adult hippocampal neurogenesis, but the exact mechanisms underlying enhanced neural precursor cell proliferation and the relative contribution of different T helper (Th) cell subsets have remained unclear. Here, we explored the proneurogenic potential of interleukin 17-producing T helper (Th17) cells, a developmentally and functionally distinct Th cell subset that is a key mediator of autoimmune neurodegeneration. We found that base-line proliferation of hippocampal precursor cells in a T cell-deficient mouse model of impaired hippocampal neurogenesis can be restored upon adoptive transfer with homogeneous Th17 populations enriched for myelin-reactive T cell receptors. In these experiments, enhanced proliferation was independent of direct interactions of infiltrating Th17 cells with precursor cells or neighboring cells in the hippocampal neurogenic niche. Complementary studies in immunocompetent mice identified several receptors for Th17 cell-derived cytokines with mRNA expression in hippocampal precursor cells and dentate gyrus tissue, suggesting that Th17 cell activity in peripheral lymphoid tissues might promote hippocampal neurogenesis through secreted cytokines.

No MeSH data available.


Related in: MedlinePlus

Impaired base-line proliferation in the hippocampus in the absence of αβ T cells.(A) Representative BrdU immunohistochemistry of the hippocampal dentate gyrus from eight week-old wild-type (A1), TCRα+/− (A2) and TCRα−/− (A3) mice, 24 hours after the first of 3 consecutive BrdU injections. Scale bar, 100 μm. (B) Quantification of BrdU+ cells in the dentate gyrus of wild-type (n = 6), TCRα+/− (n = 7) and TCRα−/− (n = 8) mice. All numbers are mean ± SEM. ANOVA, * p < 0.05.
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f1: Impaired base-line proliferation in the hippocampus in the absence of αβ T cells.(A) Representative BrdU immunohistochemistry of the hippocampal dentate gyrus from eight week-old wild-type (A1), TCRα+/− (A2) and TCRα−/− (A3) mice, 24 hours after the first of 3 consecutive BrdU injections. Scale bar, 100 μm. (B) Quantification of BrdU+ cells in the dentate gyrus of wild-type (n = 6), TCRα+/− (n = 7) and TCRα−/− (n = 8) mice. All numbers are mean ± SEM. ANOVA, * p < 0.05.

Mentions: Statistical analysis was performed with GraphPad Prism 5 software and the GraphPad web calculator (http://www.graphpad.com/quickcalcs/). A two-tailed unpaired Student’s t-test was used for analysis of the experiments shown inFigure 2. Data from the experiments shown inFigure 1 were analyzed with ANOVA followed by Dunnett’s Multiple Comparison Test. Differences were considered statistically significant at p < 0.05.


Myelin-specific T helper 17 cells promote adult hippocampal neurogenesis through indirect mechanisms.

Niebling J, E Rünker A, Schallenberg S, Kretschmer K, Kempermann G - F1000Res (2014)

Impaired base-line proliferation in the hippocampus in the absence of αβ T cells.(A) Representative BrdU immunohistochemistry of the hippocampal dentate gyrus from eight week-old wild-type (A1), TCRα+/− (A2) and TCRα−/− (A3) mice, 24 hours after the first of 3 consecutive BrdU injections. Scale bar, 100 μm. (B) Quantification of BrdU+ cells in the dentate gyrus of wild-type (n = 6), TCRα+/− (n = 7) and TCRα−/− (n = 8) mice. All numbers are mean ± SEM. ANOVA, * p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4215755&req=5

f1: Impaired base-line proliferation in the hippocampus in the absence of αβ T cells.(A) Representative BrdU immunohistochemistry of the hippocampal dentate gyrus from eight week-old wild-type (A1), TCRα+/− (A2) and TCRα−/− (A3) mice, 24 hours after the first of 3 consecutive BrdU injections. Scale bar, 100 μm. (B) Quantification of BrdU+ cells in the dentate gyrus of wild-type (n = 6), TCRα+/− (n = 7) and TCRα−/− (n = 8) mice. All numbers are mean ± SEM. ANOVA, * p < 0.05.
Mentions: Statistical analysis was performed with GraphPad Prism 5 software and the GraphPad web calculator (http://www.graphpad.com/quickcalcs/). A two-tailed unpaired Student’s t-test was used for analysis of the experiments shown inFigure 2. Data from the experiments shown inFigure 1 were analyzed with ANOVA followed by Dunnett’s Multiple Comparison Test. Differences were considered statistically significant at p < 0.05.

Bottom Line: CD4 (+) T cells provide a neuro-immunological link in the regulation of adult hippocampal neurogenesis, but the exact mechanisms underlying enhanced neural precursor cell proliferation and the relative contribution of different T helper (Th) cell subsets have remained unclear.We found that base-line proliferation of hippocampal precursor cells in a T cell-deficient mouse model of impaired hippocampal neurogenesis can be restored upon adoptive transfer with homogeneous Th17 populations enriched for myelin-reactive T cell receptors.In these experiments, enhanced proliferation was independent of direct interactions of infiltrating Th17 cells with precursor cells or neighboring cells in the hippocampal neurogenic niche.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Immunology/Immune Regulation, CRTD - Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany ; Genomics of Regeneration, CRTD - Center for Regenerative Therapies Dresden, Technische Universität Dresden, , Fetscherstraße 105, 01307 Dresden, Germany.

ABSTRACT
CD4 (+) T cells provide a neuro-immunological link in the regulation of adult hippocampal neurogenesis, but the exact mechanisms underlying enhanced neural precursor cell proliferation and the relative contribution of different T helper (Th) cell subsets have remained unclear. Here, we explored the proneurogenic potential of interleukin 17-producing T helper (Th17) cells, a developmentally and functionally distinct Th cell subset that is a key mediator of autoimmune neurodegeneration. We found that base-line proliferation of hippocampal precursor cells in a T cell-deficient mouse model of impaired hippocampal neurogenesis can be restored upon adoptive transfer with homogeneous Th17 populations enriched for myelin-reactive T cell receptors. In these experiments, enhanced proliferation was independent of direct interactions of infiltrating Th17 cells with precursor cells or neighboring cells in the hippocampal neurogenic niche. Complementary studies in immunocompetent mice identified several receptors for Th17 cell-derived cytokines with mRNA expression in hippocampal precursor cells and dentate gyrus tissue, suggesting that Th17 cell activity in peripheral lymphoid tissues might promote hippocampal neurogenesis through secreted cytokines.

No MeSH data available.


Related in: MedlinePlus