The considerable role of DCs as a functional interface between innate and acquired immunity as well as the most important stimulator of T lymphocyte responses depends on their maturation stages [1,2]. During cell activation following the transition from the immature phase to the mature DCs, an upregulation in the expression of surface costimulatory molecules including CD86, CD40, CD83 and HLA-DR is observed [3]. The maturation process of DCs stimulates the production of inflammatory cytokines. Further, the mature DCs convert the captured antigens into immunological peptides and present them as peptide-MHC-II complexes on the cell surface. The cytokine production and presence of MHC class II-peptide complexes (pMHC-II) on the surface of DCs are essential parameters for the initiation and stimulation of an adaptive immune response [[4], [5], [6]].

Previous studies have reported that increased expression of CD86 and HLA-DR in the DCs maturation stage results from a reduced expression of MARCH-I mRNA. MARCH-I is an ubiquitin E3 ligase. Ubiquitination of proteins is a significant post-translational modification that plays a remarkable role in gene transcription, protein degradation and signal transduction. Therefore MARCH-I leads to post-translational regulation of HLA-DR and CD86 molecules in APCs such as immature DCs and naïve B cells [[7], [8], [9], [10]]. MARCH-I ubiquitinates a conserved lysine residue in the cytoplasmic tail of the target chain that guide them through lysosomal degradation [11]. Following DCs activation, MARCH-I mRNA expression is suppressed and MHC-II ubiquitination is ceased [6]. IL10 is one of the direct stimulators of MARCH-I gene expression. Hence, it is proposed that the suppressive activity of IL10 in cooperation with MARCH-I is essential for the ubiquitination-mediated degradation of basic costimulatory molecules of DCs [7].

To ensure an appropriate immune response in a variety of situations from immune stimulation to suppression of exaggerated responses, the behavior of DC as a professional APC is strongly regulated [8,12]. One subset of DCs is called tolerogenic DCs which play a pivotal role in the polarization of regulatory T cells under steady state conditions [13]. In previous studies, low expression of HLA -DR, CD86, CD83 and high production of IL 10 have been reported as characteristics of tolerogenic DCs [11,14].

Gene therapy can be an effective and long-term method for manipulating of the immune system. There are several gene transfer methods, among which, viral transduction especially by lentiviruses has become more popular and practical due to their ability to integrate transgenes into non-dividing cell genomes [15,16]. Considering some points, HIV-based vectors have the ability to transduce DCs without serious changes on their immunophenotype and biological functions such as allostimulatory responses [17,27]. Therefore, researchers are interested in optimizing the parameters involved in the methods of gene delivery to the DCs. To understand the physiological role of MARCH-I on the function of DCs maturation, current study was designed to evaluate the effects of MARCH-I overexpression on the immunophenotypic characteristics and biological activity of DCs.