Abstract
CD103+ dendritic cells (DCs) have been shown to play a crucial role in the pathogenesis of inflammatory bowel diseases (IBDs) through educating regulatory T (Treg) cells differentiation. However, the mechanism of CD103+ DCs subsets differentiation remains elusive. Interleukin (IL)-4 is a pleiotropic cytokine that is upregulated in certain types of inflammation, including IBDs and especially ulcerative colitis. However, the precise role of IL-4 in the differentiation of CD103+ DCs subpopulation remains unknown. In this study, we observed a repressive role of IL-4 on the CD103+ DCs differentiation in both mouse and human. High-dose IL-4 inhibited the CD103+ DC differentiation. In comparison to CD103− DCs, CD103+ DCs expressed high levels of the co-stimulatory molecules and indoleamine 2,3-dioxygenase (IDO). Interestingly, IL-4 diminished IDO expression on DCs in a dose-dependent manner. Besides, high-dose IL-4-induced bone marrow-derived DCs, and monocyte-derived DCs revealed mature DCs profiles, characterized by increased co-stimulatory molecules and decreased pinocytotic function. Furthermore, DCs generated under low concentrations of IL-4 favored Treg cells differentiation, which depend on IDO produced by CD103+ DCs. Consistently, IL-4 also reduced the frequency of CD103+ DC in vivo. Thus, we here demonstrated that the cytokine IL-4 involved in certain types of inflammatory diseases by orchestrating the functional phenotype of CD103+ DCs subsets.
Highlights
Dendritic cells (DCs) is well known as the professional antigen-presenting cells, uptaking and processing pathogenic substance, and presenting the antigen to T cells through peptide–MHC complex [1]
There were no significant differences in the yield of Bone marrow-derived DCs (BMDCs) and monocyte-derived DCs (MoDCs) generation (Figure 1)
In comparison to dendritic cells (DCs) generated under high IL-4 concentrations, DCs generated from low IL-4 concentrations displayed an immature phenotype
Summary
Dendritic cells (DCs) is well known as the professional antigen-presenting cells, uptaking and processing pathogenic substance, and presenting the antigen to T cells through peptide–MHC complex [1]. In addition to antigens presentation, DCs play a crucial role in regulating immune response by the co-stimulatory molecules interaction, which provides the second signal in the process of T cell activation and proliferation [2]. A number of studies have shown that inhibition or depletion of costimulatory molecules on DCs can improve activity of inflammatory diseases [3,4,5,6]. Numerous studies have shown that the alteration of T cell polarization could ameliorate the development of disease. It has been shown that the presence of IL-4 in the initial DCs activation could lead to a dominant Th1 immune response, which had a protective effect in Leishmania-infected mice [16]. The DCs function altered by IL-4 might explain the mixed Th1/Th2 immune response in IBDs
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