Interleukin-10 receptor-1 expression in monocyte-derived antigen-presenting cell populations: dendritic cells partially escape from IL-10\'s inhibitory mechanisms.

von Lanzenauer SH, Wolk K, Höflich C, Kunz S, Grünberg BH, Döcke WD, Reineke U, Asadullah K, Sterry W, Volk HD, Sabat R
Source: Genes Immun
Publication Date: (2015)
Issue: 16(1): ePub
Cells used in publication:
Fibroblast, dermal (NHDF-Neo), human neonatal
Species: human
Tissue Origin: dermal
Fibroblast, dermal(NHDF-Ad), human adult
Species: human
Tissue Origin: dermal
Adipocyte (pre), human
Species: human
Tissue Origin: adipose
Keratinocyte, (NHEK-neo) human neonatal
Species: human
Tissue Origin: dermal
Interleukin (IL)-10 is one of the most crucial suppressors and regulators of the immune system, however, it only exerts its biological effects by interacting with a transmembrane receptor complex that is composed of two different receptor chains, IL-10R1 and IL-10R2. As little is known about the expression and regulation of IL-10R1, the author analyzed IL-10R1 in various cells isolated from PBMCs including blood monocytes and CD4+ T cells, cells supposed to represent the main targets of IL-10. Both cell types showed expression of both IL-10R1 and IL-10R2. By contrast, while they expressed IL-10R2, various skin derived cells not involved in the immune response including keratinocytes (from Lonza), dermal fibroblasts (from Lonza), dermal microvascular endothelial cells, subcutaneous adipocytes (from Lonza), and melanocytes showed no expression of IL-10R1.
Interleukin (IL)-10 is an important immunoregulatory cytokine that mediates its effects via a transmembrane receptor complex consisting of two different chains, IL-10R1 and IL-10R2. While IL-10R2 is ubiquitously expressed and does not bind IL-10 primarily, the expression of IL-10R1 determines cellular responsiveness. However, the current knowledge about the expression and regulation of IL-10R1 is still limited. Here we analyzed the expression of IL-10R1 on monocytic cells and demonstrated that human blood monocytes carried about 720 IL-10-binding sites on their surface. Compared with lymphocytes and various tissue cells and tissues, blood monocytes expressed the highest IL-10R1 levels. The in vitro differentiation of these cells into macrophages provoked a further increase of IL-10R1 surface expression. In contrast, their differentiation into myeloid dendritic cells (mDCs) resulted in reduced surface IL-10R1 levels. The different IL-10R1 levels expressed by monocyte-derived antigen-presenting cell populations were reflected in their different responsiveness toward IL-10. Importantly, also in vivo developed immature macrophages and mDCs showed different IL-10 sensitivity. These data suggest that, compared with monocytes and macrophages, mDCs partially escape from IL-10's inhibitory mechanisms by downregulating IL-10R1.