Modulatory Impact of Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients on T Helper Cell Differentiation

• Main Authors: Ewa Kuca-Warnawin, Iwona Janicka, Krzysztof Bonek, Ewa Kontny
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Cells
• Subjects: ankylosing spondylitis; adipose-derived mesenchymal stem cells; T helper cell subsets; transcription factors; cytokines
• Online Access: https://www.mdpi.com/2073-4409/10/2/280

The domination of pro-inflammatory Th subsets (Th1, Th17) is characteristic of ankylosing spondylitis (AS). Mesenchymal stem cells (MSC) were reported to normalize Th imbalance, but whether MSCs from AS adipose tissue (AS/ASCs) possess such properties is unknown. We examined AS/ASCs’ impact on Th-cell differentiation, using healthy donors ASCs (HD/ASCs) as a control. The assessment of the expression of transcription factors defining Th1 (T-bet), Th2 (GATA3), Th17 (RORc), and Treg (FoxP3) subsets by quantitative RT-PCR, the concentrations of subset-specific cytokines by ELISA, and Treg (CD4⁺CD25^highFoxP3⁺) formation by flow cytometry, were performed in the co-cultures of ASCs with activated CD4⁺ T cells or peripheral blood mononuclear cells (PBMCs). AS/ASCs and HD/ASCs exerted similar immunomodulatory effects. Acting directly on CD4⁺ T cells, ASCs decreased the T-bet/GATA3 and RORc/FoxP3 ratios, diminished Treg formation, but increase IFNγ and IL-17AF production, while ASCs co-cultured with PBMCs enhanced Treg generation and reduced IFNγ release. ASCs failed to up-regulate the anti-inflammatory IL-10 and TGFβ. AS/ASCs’ impact on allogeneic and autologous PBMCs was similar. In conclusion, to shift Th differentiation to a functional anti-inflammatory direction, ASCs require accessory cell support, whereas their direct effect may be pro-inflammatory. Because ASCs neither inhibit IL-17AF nor up-regulate anti-inflammatory cytokines, their usefulness for AS patients’ treatment remains uncertain.