Respective involvement of TGF-beta and IL-4 in the development of Langerhans cells and non-Langerhans dendritic cells from CD34(+) progenitors

In vivo, dendritic cells (DC) form a network comprising different populatio ns. III particular, Langerhans cells (LC) appear as a unique population of cells dependent on transforming growth factor beta (TGF-beta) for its devel opment. In this study, we show that endogenous TGF-beta is required for the development of both LC and non-LC DC front CD34(+) hematopoietic progenito r cells (HPC) through induction of DC progenitor proliferation and of CD1a( +) and CD14(+) DC precursor differentiation. We further demonstrate that ad dition of exogenous TGF-beta polarized the differentiation of CD34(+) HPC t oward LC through induction of differentiation of CD14(+) DC precursors into E-cadherin(+), Lag(+)CD68(-), and Factor XIIIa(-)LC, displaying typical Bi rbeck granules. LC generated front CD34(+) HPC in the presence of exogenous TGF-beta displayed overlapping functions with CD1a(+) precursor-derived DC . In particular, unlike CD14(+)-derived DC obtained in the absence of TGF-b eta, they neither secreted interleukin-10 (IL-10) on CD40 triggering nor st imulated the differentiation of CD40-activated naive B cells. Finally, IL-4 , when combined with granulocyte-macrophage colony-stimulating factor (GM-C SF), induced TGF-beta-independent development of non-LC DC front CD34(+) HP C, Similarly, the development of DC front monocytes with GM-CSF and IL-4 wa s TGF-beta independent. Collectively these results show that TGF-beta polar ized CD34(+) HPC differentiation toward LC, whereas IL-4 induced non-LC DC development independently of TGF-beta.