IL-4 supports the generation of a dendritic cell subset from murine bone marrow with altered endocytosis capacity

Abstract

Dendritic cells (DC) of myeloid origin can be generated from mouse bone marrow (BM) using granulocyte macrophage-colony stimulating factor (GM-CSF). Immature major histocompatibility complex (MHC) II(low) DC are known to bear a high endocytosis capacity, in contrast to DC precursors and mature DC. Now we found that a subset of MHC II(low) DC in BM-DC cultures is unable to exert mannose receptor-mediated endocytosis of fluorescein isothiocyanate (FITC)-dextran (DX) and resembles immature Langerhans cells (LC). The FITC-DX endocytosis activity of LC-like cells occurs at an earlier stage of development, where the surface MHC II expression is absent or very weak. This LC-like subset expresses higher levels of E-cadherin but lower amounts of the markers Gr-1, scavenger receptor 2F8, and CD11b, when compared with the highly endocytic DC subset. The latter myeloid DC resemble monocyte-derived DC (MoDC). The sorted LC-like population develops completely and exclusively into mature MHC IIhigh DC, and the MoDC-like cells remain immature MHC II(low) DC or develop into adherent MHC IIneg macrophages or mature into MHC IIhigh DC. The development of LC-like cells is promoted by interleukin-4. Thus, we show here that the simultaneous development of LC-like and MoDC-like DC subsets occurs in standard bulk cultures with GM-CSF, suggesting the existence of two different precursors for LC and MoDC in BM.

C5a receptor signalling in dendritic cells controls the development of maladaptive Th2 and Th17 immunity in experimental allergic asthma

“…It has been demonstrated that antigen uptake and processing correlates with the maturation status of DCs. 41,42 Our data suggest that C5aR activation during GM-CSF-mediated DC differentiation is an important signal that keeps DCs in a more immature state required for antigen sensing. We were not able to assign the decreased potency of antigen uptake to a particular endocytosis pathway.…”

Estrogen Selectively Promotes the Differentiation of Dendritic Cells with Characteristics of Langerhans Cells

“…In contrast, the CD11b Ϫ/ϩ Ly6C/G Ϫ c-Fms Ϫ population remained DC under all conditions and exhibited features of LC, with expression of E-cadherin and CD205; these DC were less capable of internalizing DexFITC and displayed greater levels of MHCII and allostimulatory capability. A second study extended these observations and divided immature MHCII int BM DC into two groups based on the ability to internalize DexFITC (27). DexFITC ϩ DC were CD11b high Ly6C/G high E-cadherin Ϫ , whereas DexFITC Ϫ DC were CD11b int Ly6C/G Ϫ E-cadherin ϩ .…”

“…The precise developmental relationship between the CD11b high Ly6C ϩ and CD11b int Ly6C Ϫ DC populations that differentiate in GM-CSF-supported BM cultures remains unclear, although the above-mentioned studies suggest that the CD11b int DC may arise via multiple pathways (27,28). We do not yet have strong evidence that one DC population arises from the other, or that the two DC populations arise from distinct undifferentiated myeloid progenitors.…”

“…In the steady state, langerin is retained primarily in endosomal recycling compartments, and BG form apparently where langerin accumulates in pericentriolar endosomes (21). Upon binding mannose or anti-langerin Abs, cell surface langerin rapidly internalizes preferentially into BG-rich, and not MHC class II (MHCII)-rich, compartments (19,21 int DC express the characteristic LC molecules E-cadherin and CD205 and are enhanced by the presence of TGF-␤ (27,28).…”

Choose your models wisely: How different murine bone marrow-derived dendritic cell protocols influence the success of nanoparticulate vaccines in vitro

“…For one, the variability of BM-DCs generated via different protocols has already lead to substantial debate on an immunological level. For instance, Lutz et al observed major differences in the immune stimulating properties of BM-DCs based on the serum and cytokine cocktails used during their differentiation from bone marrow cells [19,20].…”