Reprogrammed fibrocytes induce a mixed Th1/Th2 cytokine response of naïve CD4(+) T cells.

Naïve CD4(+) T cells develop different effector T cells and cytokine profiles after antigenic stimulation. It has been previously documented that fibrocytes function as antigen presenting cells inducing proliferation as well as Th2 cytokine response in naïve CD4(+) T cells. Our group has reported that several circulating cell types recruited to the wound site can be transformed into anti-fibrotic profile cells, which subsequently induce MMP-1 stimulation in dermal fibroblasts. Here, we report how similar reprogramming pathway of fibrocytes could modify the CD4(+) T cell response. Our findings confirmed that reprogrammed fibrocytes induce CD4(+) T cell activation with a mixed Th1/Th2 cytokine response. Since a reciprocal positive feedback between Th2 cells and fibrocytes exist to amplify and perpetuate the pro-fibrotic stimulation in dermal fibroblasts, the novel transdifferentiation of regular mature fibrocytes into reprogrammed fibrocytes appears to be a promising strategy to reverse the Th2 cytokine overproduction, and subsequently control the local fibrogenesis.