Fig. 7: TNFα couples T-lineage differentiation with IL-3-induced proliferation. | npj Regenerative Medicine

Fig. 7: TNFα couples T-lineage differentiation with IL-3-induced proliferation.

From: Multi-objective optimization reveals time- and dose-dependent inflammatory cytokine-mediated regulation of human stem cell derived T-cell development

Fig. 7

a Individually, IL-3 stimulates proliferation of myeloid-biased CD34+ HSPCs while TNFα induces T-lineage differentiation by positively regulating Notch target genes. It also increases the proportion of cells responsive to IL-3 by regulating the IL-3 receptor. When combined, IL-3 provides strong proliferative signals to developing lymphocytes, leading to substantial expansion of T-lineage cells. b The positive effects of IL-3 and TNFα are on T-cell specification where cells have limited responsiveness to IL-7. Once T-lineage development is initiated, SCF and IL-7 become the drivers of proliferation, and responsiveness to IL-3 and TNFα is lost. TNFα becomes inhibitory when cells enter developmental stages associated with positive and negative selection.

Back to article page