Up‐regulation of human epidermal Langerhans' cell B7‐1 and B7‐2 co‐stimulatory molecules in vivo by solar‐simulating irradiation

Abstract

Ultraviolet (UV) radiation impairs cutaneous immune functions and induces antigen-specific tolerance both locally at the irradiated skin site, as well as at distant skin sites and systemically. It has been postulated that in the local model, altered Langerhans' cells (LC) provide tolerogenic signals, and studies in vitro have indicated that UV radiation may down-regulate the expression of co-stimulatory molecules on the surface of these cells. To examine the effect of UV radiation on LC co-stimulatory molecules in vivo, we irradiated human volunteers with erythematogenic doses of solar-simulating UV radiation (SSR), and analyzed the expression of cell surface markers in dermatome skin samples obtained 1-72 h post-irradiation. For flow cytometric analysis, epidermal cell (EC) suspensions were prepared and double labeled with monoclonal antibodies against CD1a or HLA-DR, and B7-1 (CD80), B7-2 (CD86), ICAM-1 (CD54), ICAM-3 (CD50), LFA-3 (CD58), E-cadherin, or integrin-beta4 (CD104). In unirradiated control skin samples, keratinocytes (KC) expressed high levels of E-cadherin. LC expressed high levels of both E-cadherin and ICAM-3, and low levels of B7-2, LFA-3, ICAM-1, and integrin-beta4. Following SSR, a triphasic reaction pattern was seen: an immediate, down-regulatory phase prevailing 2-6 h post-irradiation, when the number of DR+ and CD1a+ cells were temporarily reduced; a delayed, up-regulatory phase in which the number of LC was increased and the expression intensities of CD1a, HLA-DR, B7-1, and B7-2 were strongly up-regulated, maximally evident 12-24 h after irradiation, but no more seen at 48 h; and a late phase at 72 h, in which an influx of monocytes and a concomitant rise in DR+ cells was recorded. We conclude that to understand real-life cutaneous UV immunology, studies in vitro need to be complemented with studies in vivo. In the case of LC, the effects of erythematogenic UV radiation in vivo on human LC B7 co-stimulatory molecules include an up-regulatory stage.

Solar-Simulated Ultraviolet Radiation Induces Abnormal Maturation and Defective Chemotaxis of Dendritic Cells

“…Furthermore, we have found that UV radiation increases the T cell stimulatory capability of immature DC. These data are in accordance with studies that described the upregulation of CD80 and CD86 on human epidermal LC in vivo after simulated solar radiation (Laihia and Jansen, 1997). Interestingly, it has been described that p38‐mitogen‐activated protein kinase mediates the induction of both MHC‐II and CD86 and apoptosis on human‐monocyte derived DC after UVB induction (Nakagawa et al , 2004).…”

p38 Mitogen-Activated Protein Kinase Mediates Dual Role of Ultraviolet B Radiation in Induction of Maturation and Apoptosis of Monocyte-Derived Dendritic Cells

“…This is the first report that demonstrates the activation of MoDC by UVB. Such activation has been observed in human LC irradiated in vivo or ex vivo (Laihia and Jansen, 1997;Nakagawa et al, 1999), but not when LC were firstly isolated and then irradiated in vitro (Weiss et al, 1995;Rattis et al, 1998). These discrepancies might have arisen for several reasons.…”

“…Using monocyte-derived dendritic cells (MoDC), it was demonstrated that activation of caspases 3, 8, and 9 was involved in the apoptotic processes (Nicolo et al, 2001). Some LC, however, showed maturation when they were irradiated with UVB in vivo or ex vivo (Laihia and Jansen, 1997;Nakagawa et al, 1999), but so far the mechanisms by which DC are activated by UVB have not been clear.…”

Irradiation up‐regulates CD80 expression through induction of tumour necrosis factor‐α and CD40 ligand expression on B lymphoma cells

“…Various treatments have been shown to induce or up‐regulate the expression of CD80 molecules. For example, stimulation of B cells with lipopolysaccharide, cross‐linking CD21/CD35 or CD19 on the surface of B cells 10 and solar stimulation of epidermal Langerhans cells have all been shown to increase the expression of CD80 11 . In previous studies, we reported that either partial inhibition of protein synthesis or X‐ray irradiation of the B lymphoma cells, A20‐2J, selectively enhances CD80 expression, and that this in turn results in the enhancement of their APC function 12,13 .…”