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Published on: June 22, 2016
Identification of a novel population of Langerin+ dendritic cells
Laura S Bursch1, Liangchun Wang, Botond Igyarto
1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Insights
Researchers discovered a novel population of dermal Langerhans cells (LCs) that are crucial for contact hypersensitivity (CHS) responses. This finding explains previous conflicting results regarding the role of LCs in skin immunity.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Langerhans cells (LCs) are epidermal antigen-presenting cells critical for skin immunity.
- Previous studies on LCs' role in contact hypersensitivity (CHS) yielded conflicting results due to distinct experimental models.
- The precise function of LCs in skin immune responses remained unclear.
Purpose of the Study:
- To investigate the discrepancies in LC function observed in different experimental models.
- To identify and characterize novel LC populations within the skin.
- To elucidate the specific roles of epidermal versus dermal LCs in CHS.
Main Methods:
- Comparative analysis of distinct LC depletion models (Lang-DTREGFP and hLang-DTA mice).
- Utilized diphtheria toxin to selectively deplete epidermal and dermal LCs.
- Assessed CHS responses following targeted LC depletion.
- Characterized cell surface phenotype and radiosensitivity of epidermal and dermal LCs.
Main Results:
- Identified a novel population of radio-sensitive dermal Langerin(+) dendritic cells (DCs) with a distinct phenotype.
- Dermal Langerin(+) DCs, unlike epidermal LCs, migrate to lymph nodes in both steady-state and inflammatory conditions.
- Depletion of both epidermal and dermal LCs abrogated CHS responses.
- Absence of only epidermal LCs did not affect CHS responses, indicating a key role for dermal LCs.
Conclusions:
- Dermal Langerin(+) DCs are a distinct population crucial for mediating CHS.
- This discovery reconciles conflicting findings in previous LC research.
- Highlights the importance of distinguishing between epidermal and dermal LCs in skin immunity.
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.
