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

Research output: Contribution to journalResearch articleContributedpeer-review

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 pro-proliferative 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 (TCR). 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.

Details

Original languageEnglish
Article number169
JournalF1000Research
Volume3
Publication statusPublished - 2017
Peer-reviewedYes

External IDs

ORCID /0000-0002-5304-4061/work/161408207
ORCID /0000-0001-6770-4078/work/161408835
ORCID /0000-0002-2524-1041/work/166326380

Keywords

Keywords

  • Adult neurogenesis, Cytokines, Hippocampus, Immune deficiency, Learning and memory, Plasticity, Regulatory T cells, Stem cells