Interleukin-3 in cooperation with transforming growth factor beta induces granulocyte macrophage colony stimulating factor independent differentiation of human CD34+ hematopoietic progenitor cells into dendritic cells with features of Langerhans cells.

Recently, we have reported that M-CSF in cooperation with TGF-beta1 can induce Langerhans cell (LC) development from hematopoietic progenitor cells (HPCs) without GM-CSF. In the present study, we examined whether TGF-beta1 changes the differentiation of HPCs induced by IL-3 towards LC development. We cultured HPCs in a serum-free medium in the presence of IL-3 and a combination cytokines including Flt3L, SCF, and TNF-alpha with or without TGF-beta1. DCs induced by the IL-3 culture (IL-3 DCs) did not significantly differ from those induced by the GM-CSF culture (GM-CSF DCs). Namely, both expressed CDla, F-cadherin, and Langerin in the presence of TGF-beta1 and stimulated allogeneic T cells at a similar magnitude. In contrast to GM-CSF DCs, IL-3 DCs lacked the expression of Birbeck granules (BGs) in spite of their expression of Langerin. When we compared the expression of Langerin between these two DCs, however, it became clear that both Langerin protein and mRNA were significantly lower in IL-3 DCs than in GM-CSF DCs. These studies again demonstrated the ability of TGF-beta1 to polarize the differentiation of HPCs induced by IL-3 towards LC development, although IL-3 DCs were unable to form BGs partly because of their poor ability to induce Langerin.