4,4'-diaponeurosporene, a C30 carotenoid, effectively activates dendritic cells via CD36 and NF-κB signaling in a ROS independent manner.

Haofei Liu,Tao Qin,Xiaojing Chang,Wenwen Xu,Qian Yang,Yinyan Yin

doi:10.18632/oncotarget.9800

Abstract

Carotenoids could be divided into C30 carotenoids and C40 carotenoids. The immune functions of C40 carotenoids had been extensively researched, while those of C30 carotenoids still remain unclear. In this study, the immune functions of a biosynthetic C30 carotenoid, 4,4′-diaponeurosporene (Dia), were identified on dendritic cells (DCs). DCs treated with 1 μM Dia for 24 h showed morphologic and phenotypic characteristics of mature state and had an increased production of IL-6, IL-10, IL-12p70 and TNFα, while β-carotene had a suppressive effect on DCs maturation. Moreover, Dia promoted antigen uptake of DCs in vitro and increased the quantity of antigen loaded DCs in mesenteric lymph nodes (MLN). Dia-treated DCs also had an enhanced ability to stimulate T cell proliferation and Th1 polarization. Further researches showed that Dia activated DCs via CD36 as well as ERK, JNK, and NF-κB signals in a reactive oxygen species (ROS) independent manner.

Highlights

The carotenoids, a subfamily of the isoprenoids, are among the most widespread of natural substances [1], and play important biological roles as accessory light-harvesting components of photosynthetic systems, photoprotecting antioxidants, and regulators of membrane fluidity [2]
The results showed that Dia enhanced the phosphorylation levels of extracellular signal-regulated kinases (ERK) and Jun N-terminal kinases (JNK), but not p38, while β-carotene had no notable influences on the phosphorylation of Mitogen-activated protein kinases (MAPKs) (Figure 5a)
The expression of CD80 had the tendency to reduce, though non-significant (P = 0.06) (Figure 6b). These results indicated the critical role of CD36 in Dia-induced Dendritic cells (DCs) maturation. This was the first report of which we were aware concerning the effects of C30 carotenoid on the functions of DCs

Summary

Introduction

The carotenoids, a subfamily of the isoprenoids, are among the most widespread of natural substances [1], and play important biological roles as accessory light-harvesting components of photosynthetic systems, photoprotecting antioxidants, and regulators of membrane fluidity [2]. The immune functions of many C40 carotenoids, such as β-carotene, lycopene, had been extensively researched [3,4,5,6]. While as another kind of important carotenoids, C30 carotenoids were seemingly ignored from the beginning. Dendritic cells (DCs) are potent antigen-presenting cells that play a major role in the initiation and regulation of the immune response [7]. In response to a spectrum of stimuli, iDCs undergo a maturation process by up-regulating the expression of MHCII and co-stimulatory molecules, as well as the production of cytokines, greatly enhancing their ability to active T cells [9]

Methods

Results

Conclusion