In vitro treatment of human transforming growth factor‐β₁‐treated monocyte‐derived dendritic cells with haptens can induce the phenotypic and functional changes similar to epidermal Langerhans cells in the initiation phase of allergic contact sensitivity reaction

Abstract

SUMMARYHuman monocyte-derived dendritic cells (MoDCs) obtained from peripheral blood monocytes (PBMC) cultured with granulocyte±macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) can be activated in vitro by a variety of simple chemicals such as haptens and several metals. Recently, it has been demonstrated that transforming growth factor-b 1 (TGFb 1 ) can induce further differentiation of MoDCs to the cells that share some characteristics with epidermal Langerhans cells, i.e. they contain Birbeck granules and express E-cadherin. In this study, using such TGF-b 1 -treated dendritic cells (TGF-b 1 + DCs), we examined the in vitro effects of representative haptens, i.e. NiCl 2 and dinitrochlorobenzene (DNCB), on their phenotypic and functional characteristics, comparing with those reported in vivo in epidermal Langerhans cells during the sensitization phase of a contact sensitivity reaction. Treatment of TGF-b 1 + DCs with NiCl 2 increased their expression of the molecules related to antigen presentation such as CD86, major histocompatibility complex class I and class II, and CD83, although weakly, in addition to that of those essential for their migration to the regional lymph nodes, such as CD49e, CD44 and its variant 6, while it down-regulated the expression of the molecules required for homing to the skin and staying in the epidermis, such as cutaneous leucocyte antigen (CLA) and E-cadherin. It also increased the production of tumour necrosis factor-a, but not that of IL-1b or IL-12. DNCB also increased their CD86 expression and down-regulated E-cadherin and CLA, but did not affect other phenotypic changes that were observed in TGF-b 1 + DCs treated with NiCl 2 . TGF-b 1 + DCs treated with either NiCl 2 or DNCB increased their allogeneic T-cell stimulatory function. In addition, reverse transcribed polymerase chain reaction revealed augmented expression of chemokine receptor 7 mRNA by TGF-b 1 + DCs when treated with either NiCl 2 or DNCB. Moreover, consistent with this data, TGF-b 1 + DCs treated with these chemicals chemotactically responded to macrophage in¯ammatory protein-3b. These data suggest the possibility that TGF-b 1 + DCs present a good in vitro model to study the biology of epidermal Langerhans cells.

Present and future ofin vitroimmunotoxicology in drug development

“…The establishment of human in vitro models of DC had offered the possibility to demonstrate that haptens were able to directly activate cultured DC derived from peripheral blood monocytes or from CD34 + HPC (Aiba et al, 1997;Degwert et al, 1997;Rougier et al, 2000;De Smedt et al, 2001;Weigt et al, 2004). Several studies confirmed these observations showing the upregulation of maturation markers (CD83, CD80, CD86, CD40) on human DC (Coutant et al, 1999;Aiba et al, 2000;Tuschl et al, 2000;Arrighi et al, 2001). Cytokine production such as IL-12p40, TNF-α, and IL-1β has also been reported upon hapten stimulation (Aiba et al, 1997(Aiba et al, , 2003De Smedt et al, 2001).…”

Effect of Skin Sensitizers on Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Skin Dendritic Cells: Role of Different Immunosuppressive Drugs

“…This hapten increases the expression of DC surface markers essential for antigen presentation, such as the molecules of the major histocompatibility complex class II and costimulatory molecules (4)(5)(6)(7)(8)(9)(10) and increases chemokine production and chemokine receptor expression (11)(12)(13)(14) , thereby favoring antigen presentation. In DC, contact sensitizers activate mitogen-activated protein kinases (15)(16)(17)(18)(19)(20)(21) . We previously have reported that nickel sulfate activates the transcription nuclear factor kappa B (NF-kB) and the transcription factor activator protein-1 (AP-1) and induces the expression of inducible isoform of nitric oxide synthase (iNOS) in mouse skin DC (22) .…”

Gene Expression Changes Induced by Type IV Allergy-Inducible Chemicals in Dendritic Cells

“…However, the use of in vitro differentiated primary DCs is difficult due to the nature of these cells such as low numbers in the source and donor-todonor variability [2]. In addition, treatment with several cytokines is generally applied to obtain DCs from blood or bone marrow cells [3,11,30], and this process probably changes the cell reactivity to stimulations. Thus, established cell lines are preferable to standardize the condition among assay.…”