Abstract
CCL-34, a synthetic α-galactosylceramide analog, has been reported as an activator of toll-like receptor 4 (TLR4) in macrophages. TLR4 is highly expressed in dendritic cell (DC) and several TLR4 agonists are known to trigger DC maturation. We herein evaluated the effect of CCL-34 on DC maturation. Human CD14+ monocyte-derived immature DC were treated with CCL-34, its inactive structural analog CCL-44, or LPS to assess the DC maturation. CCL-34 induced DC maturation according to their characteristically dendrite-forming morphology, CD83 expression and IL-12p70 production. The allostimulatory activity of DC on proliferation of naive CD4+CD45+RA+ T cells and their secretion of interferon-γ was increased by CCL-34. Phagocytosis, an important function of immature DC, was reduced after CCL-34 treatment. All these effects related to DC maturation were evidently induced by positive control LPS but not by CCL-44 treatment. TLR4 neutralization impaired human DC maturation triggered by CCL-34. The induction of IL-12, a hallmark of DC maturation, by CCL-34 and LPS was only evident in TLR4-competent C3H/HeN, but not in TLR4-defective C3H/HeJ mice. CCL-34 could further elicit the antigen presentation capability in mice inoculated with doxorubicin-treated colorectal cancer cells. In summary, CCL-34 triggers DC maturation via a TLR4-dependent manner, which supports its potential application as an immunostimulator.
Highlights
dendritic cell (DC) are specialized leukocytes that present antigens to naive T cells, playing a pivotal role in bridging cell-mediated and humoral immune responses in vivo [1]
When CCL-34 was added into culture of immature DC to trigger maturation, there was no significant effect on recovery rate of DC, as measured by trypan blue exclusion test (Figure 2A)
Because CCL-34 has been reported as a Toll-like receptor 4 (TLR4) activator in our previous work, we evaluated whether the effect of CCL-34 on DC maturation is dependent on TLR4
Summary
DC are specialized leukocytes that present antigens to naive T cells, playing a pivotal role in bridging cell-mediated and humoral immune responses in vivo [1]. The ability of DC to stimulate T cells is mainly attributed to their ability to capture antigens, migrate into lymphoid organs, and express high levels of immunostimulatory molecules, such as major histocompatibility complex (MHC) class II, B7.1 (CD80), B7.2 (CD86), and IL-12 [1]. Toll-like receptor 4 (TLR4) activation on antigen presenting cells (APCs) can enhance immune responses to antigens and augment the effectiveness of vaccines [6,7,8]. Glycolipid-based TLR4 agonists, such as monophosphoryl lipid A (MPL) and RC-529, have been successfully developed as adjuvant for vaccination. These agents are potent TLR4 activators with better toxicity profile compared with LPS [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
