Roles of lactoferrin in human DC differentiation

We obtained data on the influence of bLf, whose immunomodulant properties are now recognized, on MDDC differentiation/activation. We found that bLF interferes with the activation of MD-DC induced by different TLR agonists, but not by T cell mediated signals. Although bLF did not significantly influence monocyte differentiation in DCs, we found that it markedly reduced the up-modulation of CD83, co-stimulatory and MHC molecules (i.e. CD80, CD86, MHC class I and II), and cytokine secretion (IL-12, TNF-? and IL-23) induced by LPS or polyI-C. Consistently with an impaired MDDC maturation, bLF exposed cells retained antigen uptake capacity and exhibited a lower capacity to promote T cell proliferation and Th1 polarization. Although bLF did not affect the phenotype of R848 activated MDDC, these cells exhibited a reduced capacity to produce IL-12 and TNF-? and to promote Th1 polarization, and retained antigen uptake capacity. In contrast, no major effects on the phenotypic and functional properties of CD40L activated MD-DCs were observed in the presence of bLF. Overall, these results provide evidence for an antinflammatory role of bLF in the modulation of MDDC function, independently of its capacity to bind LPS (Puddu et al.). Of note, human recombinant Lf (Talactoferrin) has been shown to exhibit different effects on human MDDC, since exposure of these cells to talactoferrin provides an activation stimulus leading to enhanced Th1 responses and production of effector cytokines. These different effects are likely due to the recognition of different receptors, expressed in MDDC by talactoferrin and bLf.

Future studies will focus on:
(1a) investigating bLf effects on DC activation triggered by TLR agonists in terms of:
i) migratory capacity,
ii) chemokine receptors expression (CCR5 versus CCR7),
iii) chemokine secretion;
(1b) characterizing mechanisms underlying the capacity of bLf to attenuate inflammation and to define whether this property is linked to its function in the regulation of iron homeostasis;
(1c) analysis of the cellular determinants involved in the interaction of MDDC with bLf as well as of their role in mediating the antinflammatory activity of bLf.

• molecule type
• lipopolysaccharide,
• Major histocompatibility complex class II,
• Biomaterial,
• Tumor necrosis factor,
• CD40 ligand,
• Toll like receptor,
• Major histocompatibility complex class I,
• Interleukin-10,
• Interleukin-12 cytokine,
• Interferon gamma,
• Interleukin-12 p40,
• CD83,
• CD86,
• CD80

• stimulus type
• Lactoferrin

• organism type
• Homo sapiens

• cell type
• T cell,
• T helper cell 1

• experimental design type
• development or differentiation experiment

created over 16 years ago (2 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF ]   [ RelFinder ]