Induction of the sphingosine-1- phosphate signaling pathway by TGF-β1 during Langerhans-type dendritic cell differentiation

摘要

Langerhans-type DCs (LCs) form dense cellular networks within basal and suprabasal keratinocyte layers of stratified epithelial tissues such as epidermis and oral mucosa. The cytokine TGF-β1 plays a critical role in LC differentiation. The addition of TGF-β1 to cytokine supplemented serum-free cultures of hematopoietic progenitor cells redirects monocyte to LC differentiation [1]. Moreover, TGF-β1 induces LC characteristics when added to cultures of monocytes, dermal CD14+ cells, and CD1c+ peripheral blood DCs. Monocytes can also give rise to GM-CSF/IL-4-dependent inflammation-associated monocyte-derived (mo)DCs [2]. However, these cells do not require exogenous TGF-β1 for their in vitro differentiation. In addition to its LC lineage instructive role, constitutive active-canonical TGF-β1 signaling counteracts LC maturation, critical for the epidermal residency of LCs [3].