Immunological modulation following bone marrow-derived mesenchymal stromal cells and Th17 lymphocyte co-cultures

Inflamm Res. 2019 Mar;68(3):203-213. doi: 10.1007/s00011-018-1205-0. Epub 2018 Nov 30.

Abstract

Objective and design: The objective of the study is to uncover the influence of human bone marrow-derived mesenchymal stem cells (BM-MSCs) on the generation of Th17 lymphocytes in co-cultures of both BM-MSCs and T cells.

Materials and methods: BM-MSCs, characterized according to the international society for cellular therapy (ISCT) criteria, were co-cultured with T cells isolated from peripheral blood. The expression levels of IL-17 receptor, RORγt and IL-23 receptor were evaluated using flow cytometry. The levels of cytokines involved in Th17 immunomodulation were measured using multiplex assay.

Treatment: Inflammatory primed and non-primed BM-MSCs were co-cultured with either activated or non-activated T cells either at (1/80) and (1/5) ratio respectively.

Results: MSC/T-cell ratio and inflammation significantly influenced the effect of BM-MSCs on the generation of Th17 lymphocytes. Cocultures of either primed or non-primed BM-MSCs with activated T cells significantly induced IL-17A-expressing lymphocytes. Interestingly, the expression of the transcription factor RORγt was significantly increased when compared to levels in activated T cells. Finally, both cell ratio and priming of BM-MSCs with cytokines substantially influenced the cytokine profile of BM-MSCs and T cells.

Conclusion: Our findings suggest that BM-MSCs significantly modulate the Th17 lymphocyte pathway in a complex manner.

Keywords: Co-culture; Cytokines; IL-23R; MSCs; ROR-γt; T cells; Th17.

MeSH terms

  • Bone Marrow Cells / cytology
  • Coculture Techniques
  • Cytokines / immunology
  • Humans
  • Mesenchymal Stem Cells / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Receptors, Interleukin / immunology
  • Th17 Cells / immunology*

Substances

  • Cytokines
  • IL23R protein, human
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Interleukin