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Updated: Jun 15, 2026

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Interplay between CD45RA+ regulatory T cells and TNF-alpha in the regulation of human Th17 differentiation
Nobuyasu Baba1, Manuel Rubio, Marika Sarfati
1Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), University of Montreal, Montreal, Quebec, Canada.
Abstract:
The balance between effector CD4(+) T cells secreting IL-17 (T(h)17) and regulatory T cells (Treg) plays an important role in autoimmune disorders that include rheumatoid arthritis (RA) and Crohn's disease. Tumor necrosis factor (TNF)-alpha is a key pro-inflammatory cytokine that contributes to disease pathogenesis. We investigated the interplay between CD45RA(+) Treg and TNF-alpha in the regulation of human T(h)17 differentiation. We found that CD45RA(+) Treg promoted while TNF-alpha inhibited naive CD4(+) T-cell differentiation into IL-17 and CCL20 co-expressing T(h)17 cells without influencing their IL-22 release. Unexpectedly, CD45RA(+) Treg depletion abrogated TNF-alpha suppressive function. Finally, dendritic cell-derived TNF-alpha suppressed the development of IL-17(+)CCL20(+) expressing T(h)17 cells. In conclusion, CD45RA(+) Treg positively governs human T(h)17 development, which is impaired by TNF-alpha. We propose that TNF-alpha may represent a negative feedback mechanism to control IL-17/CCL20- but not IL-22-associated autoimmune pathologies.
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