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Mesenchymal stromal cells inhibit Th17 but not regulatory T-cell differentiation

Raine Tatara1, Katsutoshi Ozaki, Yuji Kikuchi

  • 1Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan.

Cytotherapy
|December 22, 2010
PubMed
Abstract

Insights

Mesenchymal stromal cells (MSC) inhibit T helper 17 cell differentiation but not regulatory T-cell differentiation. MSCs suppress Th17 differentiation via prostaglandin E2 and indoleamine-2,3-dioxygenase, not nitric oxide.

Area of Science:

  • Immunology
  • Cell Biology
  • Stem Cell Research

Background:

  • Mesenchymal stromal cells (MSC) produce nitric oxide (NO), inhibiting T-cell proliferation and STAT 5 phosphorylation under neutral and T helper 1 (Th1) conditions.
  • The immunomodulatory effects of MSC on other T-cell subsets, specifically T helper 17 (Th17) and regulatory T-cell (T-reg) populations, require further investigation.

Purpose of the Study:

  • To investigate the impact of mouse MSC on the differentiation of Th17 and T-reg cells.
  • To elucidate the mechanisms by which MSC influence T-cell subset differentiation.

Main Methods:

  • CD4 T cells from mouse spleen were cultured under Th17 or T-reg differentiating conditions, with or without mouse MSC.
  • Flow cytometry was used to assess Th17 and T-reg differentiation, measuring interleukin-17 (IL-17) and forkhead box P3 (Foxp3) expression, respectively.

Main Results:

  • MSC significantly inhibited Th17 cell differentiation.
  • MSC did not affect T-reg cell differentiation.
  • Inhibition of Th17 differentiation by MSC was partially mediated by prostaglandin E2 (PGE2) and indoleamine-2,3-dioxygenase (IDO), as their inhibitors restored differentiation.
  • MSC did not produce NO under Th17 differentiation conditions.

Conclusions:

  • MSC differentially regulate CD4 T-cell differentiation based on the specific subset and culture conditions.
  • The mechanisms of MSC-mediated immune modulation vary, involving PGE2 and IDO in the suppression of Th17 differentiation.

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