Langerhans Cells Serve as Immunoregulatory Cells by Activating NKT Cells

Abstract

Ultraviolet exposure alters the morphology and function of epidermal Langerhans cells (LCs), which play a role in UV-induced immune suppression. It is generally believed that UV exposure triggers the migration of immature LCs from the skin to the draining lymph nodes (LNs), where they induce tolerance. However, because most of the previous studies employed in vitro UV-irradiated LCs, the data generated may not adequately reflect what is happening in vivo. In this study, we isolated migrating LCs from the LNs of UV-irradiated mice and studied their function. We found prolonged LC survival in the LNs of UV-irradiated mice. LCs were necessary for UV-induced immune suppression because no immune suppression was observed in LC-deficient mice. Transferring LCs from UV-irradiated mice into normal recipient animals transferred immune suppression and induced tolerance. We found that LCs colocalized with LN NKT cells. No immune suppression was observed when LCs were transferred from UV-irradiated mice into NKT cell-deficient mice. NKT cells isolated from the LNs of UV-irradiated mice secreted significantly more IL-4 than NKT cells isolated from nonirradiated controls. Injecting the wild-type mice with anti–IL-4 blocked the induction of immune suppression. Our findings indicate that UV exposure activates the migration of mature LC to the skin draining LNs, where they induce immune regulation in vivo by activating NKT cells.

Altered Immunity and Dendritic Cell Activity in the Periphery of Mice after Long-Term Engraftment with Bone Marrow from Ultraviolet-Irradiated Mice

“…The UVR-induced effect on contact hypersensitivity responses measured only after 84 d was not significant. This is similar to a recent report (36), although these mice were sensitized at the UV-irradiated site (local UVR-induced immunosuppression). All studies confirm the longlasting effects of UVR.…”

Effects of ultraviolet radiation on Langerhans cells

“…In Bacci et al's experiment with mice irradiated with UVB, it occurred only after 24 hours [21]. However, in Fukunaga et al's study, after UVB irradiation of mice with a dose of 1000-2000 J/m 2 , the number of LCs in the epidermis returned to baseline after 63 days [22].…”

“…This phenomenon may be partly explained by the decreased expression of alpha4 integrin by LCs and its impaired binding to fibronectin as well as the reduction in surface chemokine receptor CCR7. In the study involving mice in vivo, Fukunaga et al [22] showed that exposure to UVB (270-290 nm) triggered the migra-tion of mature LC to the skin draining lymph nodes. The authors also observed prolonged LCs survival in the lymph nodes, i.e.…”

“…It is considered that UV exposure triggers the migration of LCs from the skin to the draining lymph nodes where they are responsible for inducing immune tolerance [22]. One of its manifestations is the inhibition of contact hypersensitivity (CHS) reaction in the skin exposed to UV radiation.…”

Fotoimmünoloji

“…Langerhans hücreleri lenf bezlerinde NKT hücreleriyle birliktedir ve yakınında yer alırlar. UV ışımasını takiben lenf bezlerine göç eden CD1d+ Langerhans hücreleri orada, IL-4 sekresyonu yapmaları için NKT hücrelerini uyarırlar 32 . UV ışıması yapılmış farelerden alınan haptenle konjuge Langerhans hücreleri NKT hücreleri olmayan hayvanlara (CD1-/-ya da Jα18-/-fareler) injekte edildiğinde immunsupresyon oluşturulabilir 2 .…”