The Mandatory Role of IL-10–Producing and OX40 Ligand-Expressing Mature Langerhans Cells in Local UVB-Induced Immunosuppression

Abstract

The mechanism underlying the local UVB-induced immunosuppression is a central issue to be clarified in photoimmunology. There have been reported a considerable number of cells and factors that participate in the sensitization phase-dependent suppression, including Langerhans cells (LCs), regulatory T cells, IL-10, and TNF-α. The recent important finding that LC-depleted mice rather exhibit enhanced contact hypersensitivity responses urged us to re-evaluate the role of LCs along with dermal dendritic cells (dDCs) in the mechanism of UVB-induced immunosuppression. We studied the surface expression of OX40 ligand (OX40L) and the intracellular expression of IL-10 in LCs and dDCs from UVB-irradiated (300 mJ/cm2) skin of BALB/c mice and those migrating to the regional lymph nodes from UVB-irradiated, hapten-painted mice. In epidermal and dermal cell suspensions prepared from the UVB-irradiated skin, LCs expressed OX40L as well as CD86 and produced IL-10 at a higher level than Langerin‒ dDCs. The UVB-induced immunosuppression was attenuated by the administration of IL-10–neutralizing or OX40L-blocking Abs. In mice whose UVB-irradiated, hapten-painted skin was dissected 1 d after hapten application, the contact hypersensitivity response was restored, because this treatment allowed dDCs but not LCs to migrate to the draining lymph nodes. Moreover, LC-depleted mice by using Langerin-diphtheria toxin receptor–knocked-in mice showed impaired UVB-induced immunosuppression. These results suggest that IL-10–producing and OX40L-expressing LCs in the UVB-exposed skin are mandatory for the induction of Ag-specific regulatory T cells.

Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells

“…Indeed, at steady state, LCs migrate continuously to draining LNs, presumably to induce or maintain tolerance to self or innocuous environment antigens (Ag) (22,23). In line with this hypothesis, LCs were recently shown to act as negative regulators of the anti-Leishmania response (24), to contribute to UV-induced suppression of CHS (25,26), and to dampen CHS response by a process involving IL-10 and cognate interactions with CD4 + T cells (27). Yet whether and how LCs may prevent initiation of ACD upon skin contact with weak allergens is unknown.…”

Conditional Deletion of TGF-βR1 Using Langerin-Cre Mice Results in Langerhans Cell Deficiency and Reduced Contact Hypersensitivity

“…Accumulating data suggest distinct roles for the different Langerin + DC subsets in specific immunological settings. For example, epidermal LC act as negative regulators of the anti-Leishmania response and are required for UV radiation (UVR)-induced immunosuppression (17)(18)(19). A report claiming that LC are dispensable for UVR-induced suppression of contact hypersensitivity (CHS) remains questionable, because the UVR treatment failed to mobilize the cells from the epidermis (20).…”

Fotoimmünoloji

“…Aynı zamanda UV ışıması Langerhans hücreleri üzerinde bulunan CD80/86 molekül ekspresyonunu da azalttığı için allojenik T hücreleri uyarılamaz 3 . Yoshiki ve arkadaşları 20 , UVB'ye bağlı immünsupresyonda IL-10 üreten ve OX40L eksprese eden Langerhans hücrelerinin, antijen spesifik regülatör T hücrelerinin uyarılması açısından zorunlu olduğunu bildirmişlerdir. RegülatörThücreleriveUVışıması Regülatör T hücreleri periferal toleransla ilişkili bir T hücre alt tipidir.…”