Caspase 3 may participate in the anti-tumor immunity of dendritic cells
Introduction
As the sentinel of immune system and the most potent professional specific antigen presenting cells, DCs play critical roles in the immunosurveillance in vivo [1]. Although the quantity is small, DCs spread throughout the body, including tissues and circulation [2], constantly monitoring their surroundings for different antigens [3]. In the steady state, DCs are largely immature [4], which is characterized by low expression of major histocompatibility complex (MHC) II, co-stimulatory molecules (CD80 and CD86) and chemokine receptor, and high capacity of antigen capture [5]. After antigen encounter and uptake, immature DCs become mature and the co-stimulatory molecules were upregulated [6]. Then, they migrate into secondary lymphoid organs to initiate immune responses [7].
Caspases are proteolytic enzymes which mediate the programmed cell death known as apoptosis, and they are highly conserved among different species [8]. The family of caspases can be further classified as initiator (caspases 8, 9, 10) and executioner (caspases 3, 6, 7) [9]. In principle, caspases could be activated through either extrinsic or intrinsic signal transduction pathways [10]. Upon activation, the initiator cleaves the executioner. These proteases then degrade structural substrates and DNA repair enzymes, etc. Among these executioners, caspase 3 is extremely important as both intrinsic and extrinsic pathways converge at caspase 3 [11]. In addition to the classical role in apoptosis, emerging evidence indicates that caspase 3 also execute nonapoptotic functions [12]. However, the regulation of caspase 3 on the differentiation and function of DCs has not been fully elucidated yet.
Previously, we found that the number of CD11c+MHCII+ dendritic cells was significantly decreased in caspase 3 gene knockout mice [13]. Thus, we speculate that caspase 3 may participate in the regulation of maturation and antitumor function of DCs. The present study aims to investigate the role of caspase 3 on the antitumor function of DCs.
Section snippets
Mice and cells
C57BL/6 Mice (male, 7–8 weeks old) were obtained from Animal Recourses Center of the Fourth Military Medical University. All mice were maintained in the specific pathogen-free (SPF) conditions. All animal experiments were approved by the Animal Experiment Administration Commission of Fourth Military Medical University.
DC2.4 cell line [14] was purchased from Huiying biological technology (China). Mouse melanoma (B16) cell line was gift from Dr. Y. Z. Chen. All the cells were cultured in
Overexpression of caspase 3 gene slightly influenced the biological behavior of DC2.4 cells
To establish a cellular model to gain of function of Caspase 3 gene, a lentivirus infection system was employed. RT-PCR and western blotting results showed that caspase 3 mRNA levels (Fig. 1A) and protein levels (Fig. 1B and C) significantly increased, demonstrated that the overexpression of Caspase 3 gene in DC2.4 cells were successful.
Since caspase 3 plays a key role in apoptosis, we then analyzed the proliferation and apoptosis profile of DC2.4 cells after lentivirus infection. As shown in
Discussion
DCs were initially reported by Langerhans in 1868 and then identified by Steinman in 1973 [17]. Since methods for in vitro culture of DCs were established and developed, investigation about DCs were largely accelerated [18]. As DCs could initiate specific immune responses against antigens, many studies have focused on the application of DC vaccines to treat cancer. Although DC vaccination is considered to be a potent treatment for tumor immunotherapy, it has not been as effective as expected
Conflicts of interest
The authors declare no conflict of interest.
Acknowledgements
This work was supported by the grants from National Natural Science Foundation of China (No. 31570907, No.81572306).
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Jinqiang Liu, Fei Wang and Dandan Yin contributed equally to this work.