Identification of a novel population of Langerin+ dendritic cells

Abstract

Langerhans cells (LCs) are antigen-presenting cells that reside in the epidermis of the skin and traffic to lymph nodes (LNs). The general role of these cells in skin immune responses is not clear because distinct models of LC depletion resulted in opposite conclusions about their role in contact hypersensitivity (CHS) responses. While comparing these models, we discovered a novel population of LCs that resides in the dermis and does not represent migrating epidermal LCs, as previously thought. Unlike epidermal LCs, dermal Langerin+ dendritic cells (DCs) were radiosensitive and displayed a distinct cell surface phenotype. Dermal Langerin+ DCs migrate from the skin to the LNs after inflammation and in the steady state, and represent the majority of Langerin+ DCs in skin draining LNs. Both epidermal and dermal Langerin+ DCs were depleted by treatment with diphtheria toxin in Lang-DTREGFP knock-in mice. In contrast, transgenic hLang-DTA mice lack epidermal LCs, but have normal numbers of dermal Langerin+ DCs. CHS responses were abrogated upon depletion of both epidermal and dermal LCs, but were unaffected in the absence of only epidermal LCs. This suggests that dermal LCs can mediate CHS and provides an explanation for previous differences observed in the two-model systems.

Insights into Langerhans cell function from Langerhans cell ablation models

“…Initial studies with the Dutch and French Langerin-DTR-EGFP models demonstrated that DT treatment efficiently ablated LC in the epidermis, as well as LC and blood-derived CD8 1 Langerin lo DC in the CLN. Contrary to expectation it was observed that the reconstitution of Langerin 1 DC populations in CLN preceded the reconstitution of LC in the epidermis by a couple of weeks and reappeared with similar kinetics to the blood-derived CD8 1 Langerin lo DC [30,35]. This suggested that either LC were capable of homing to CLN without trafficking through the epidermis or that another Langerin 1 DC subset existed.…”

“…It is likely that rather than intrinsic differences between the two mouse lines, differences in CHS experimental technique account for the different results. The choice of hapten does not seem to be critical since the Dutch mice also have reduced CHS to oxazalone [35]. Rather, it appears that the timing of DT administration can affect the outcome since French mice treated with DT only on day À1 develop diminished CHS responses similar to the Dutch mice [36,37].…”

“…This suggested that either LC were capable of homing to CLN without trafficking through the epidermis or that another Langerin 1 DC subset existed. Although Langerin 1 MHC class II 1 DC in the dermis had already been observed, they were always assumed to be transitory LC migrating from the epidermis to the draining LN [30,35]. Utilizing the three available mouse models (French, American and Dutch mice) and a variety of techniques, three groups were able to demonstrate the presence of a radio-sensitive Langerin-expressing dDC subset, which is independent of epidermal LC.…”

Langerhans cells and viral immunity

“…In some cases dermal DC may play the immunostimulatory role previously attributed to LC [10][11][12]. Recently, a distinct subset of dermal DC was identified in mouse that expresses langerin and this subset might be important for immunostimulation [13][14][15] although so far, little is known about their function and whether a similar subset exists in humans. LC probably play a pivotal role in certain virus infections.…”

Le derme de la peau s’enrichit d’une nouvelle population de cellules dendritiques

“…Par ailleurs, les travaux de Ginhoux et al [6] ont montré que les DDC langérine + avaient la capacité de capturer des antigènes exprimés au niveau cutané et de les véhiculer au niveau des ganglions lymphatiques cutanés. En complément de ces études, les travaux de Bursch et al, [7] ont montré que les DDC langérine + étaient à elles seules capables de contribuer au développement de réactions d'hypersensibilité de contact.…”