A Novel Role for IL-3: Human Monocytes Cultured in the Presence of IL-3 and IL-4 Differentiate into Dendritic Cells That Produce Less IL-12 and Shift Th Cell Responses Toward a Th2 Cytokine Pattern

Abstract

Dendritic cells (DC) derived from plasmacytoid precursors depend on IL-3 for survival and proliferation in culture, and they induce preferentially Th2 responses. Monocytes express not only GM-CSF receptors, but also IL-3Rs. Therefore, we examined whether IL-3 had an effect on the functional plasticity of human monocyte-derived DC generated in a cell culture system that is widely used in immunotherapy. DC were generated with IL-3 (instead of GM-CSF) and IL-4. Yields, maturation, phenotype (surface markers and Toll-like receptors), morphology, and immunostimulatory capacity were similar. Only CD1a was differentially expressed, being absent on IL-3-treated DC. In response to CD40 ligation DC generated in the presence of IL-3 secreted significantly less IL-12 p70 and more IL-10 compared with DC grown with GM-CSF. Coculture of naive allogeneic CD4+ T cells with DC generated in the presence of IL-3 induced T cells to produce significantly more IL-5 and IL-4 and less IFN-γ compared with stimulation with DC generated with GM-CSF. These data extend the evidence that different cytokine environments during differentiation of monocyte-derived DC can modify their Th cell-inducing properties. A hitherto unrecognized effect of IL-3 on DC was defined, namely suppression of IL-12 secretion and a resulting shift from Th1 toward Th2.

The immunomodulator FTY720 interferes with effector functions of human monocyte‐derived dendritic cells

“…Petri dishes were coated for 1 h with AffiniPure goat antimouse IgG (10 lg/ml; Jackson ImmunoResearch Laboratories, Avondale, PA). CD4 + CD45RA + naive T cells were isolated using a panning technique as described [38]. FACS analysis of the generated cells with anti-CD45RA mAb (BD PharMingen) showed >95% positive cells.…”

Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response

“…For instance, many inflammatory mediators such as IFN-a [20][21][22] have been shown to differentiate DC progenitors into Th1-inducing cells (herein named DC1), whereas IL-3 or PGE 2 favor DC2 [23,24]. In addition, vitamin D 3 and TGF-b induce the differentiation of DC able to induce the development of IL-10-producing regulatory T cells [25,26].…”

Important role of interleukin‐3 in the early phase of collagen‐induced arthritis

“…In monocyte/macrophages, IL-3 upregulates class II major histocompatibility complex expression and enhances lipopolysaccharide (LPS)-induced IL-1 secretion (13,14). Together with IL-4 or interferon-␤ (IFN␤), IL-3 supports differentiation of monocytes into dendritic cells (15,16). Induction of osteoclast-like cells by IL-3 has also been described (17,18).…”