Abstract
Langerhans cells (LCs) are suspected to initiate inflammatory immune responses to contact allergens and pathogenic bacteria. In chronic infectious diseases, programmed death ligand (PD-L) 1 exhibits both inhibitory and costimulatory functions on T cell-mediated activation and tolerance. Here, we investigated the effects of contact allergens and bacterial stimuli on PD-L1 expression in LCs and the effects of altered PD-L1 expression on cytokine release of subsequently cocultured T cells. Monocyte-derived LCs (MoLCs), LCs, and skin sections of patients suffering from allergic contact dermatitis were challenged with nickel and then analyzed for PD-L1 expression by confocal laser scanning microscopy and flow cytometry. In blocking experiments, we found that the release of Th cell specific cytokines was dependent on both stimulation of LCs and inhibition of PD-L1-PD-1 interactions. Stimulation with peptidoglycan (PGN) or lipopolysaccharide (LPS) and blockage of PD-L1 with a specific antibody triggered the release of high levels of IL-17, IL-22, TNF-α, and IFN-γ in CD4+T cells. If nickel was used as a stimulus, blockage of PD-L1 led to high amounts of TNF-α and IL-22. A closer look revealed PD-L1-dependent upregulation of IL-17 secretion in FACS-sorted CCR6+/CCR4+ T memory cells. In the presence of anti-PD-L1, PGN induced secretion of IFN-γ and IL-17 in total CCR6+ cells, while nickel triggered secretion of IFN-γ and IL-17 exclusively in CCR6+/CCR4+ cells. Our findings suggest that PD-L1 on LCs plays a crucial role in type IV allergic reactions and in response to bacterial stimuli by controlling the nature of inflammatory Th cell responses.
Highlights
Inflammatory responses to bacterial pathogens and allergic contact dermatitis (ACD) have in common that distinct subsets of Th cells are crucially involved
In Langerhans cells (LCs) and Monocyte-derived LCs (MoLCs) PD-L1 was found to colocalize with langerin, with bright signals for PD-L1 especially in epidermal LCs isolated from healthy individuals (Figure 1A)
In skin biopsy sections derived from local lesions of ACD patients constitutive PD-L1 expression was demonstrated in HLA-DR positive cells located in the suprabasal and upper epidermal layers (Figure 1B)
Summary
Inflammatory responses to bacterial pathogens and allergic contact dermatitis (ACD) have in common that distinct subsets of Th cells are crucially involved. Whereas the involvement of cytotoxic T cells becomes clearly evident in light of the skin lesions induced, most functional subsets of CD4+Th cells could be involved in allergic reactions. IL-22 and IL-17 have been shown to mediate protection and defense against bacteria such as Citrobacter rodentium and Klebsiella pneumoniae, and Mycobacterium tuberculosis and Bordetella pertussis, respectively [6,7,8,9]. In experimental models even parts of the bacterial cell wall, such as LPS, were shown to induce IL-22 secretion in T cells [4]. Little is known on the exact role of these Th cell subpopulations in inflammatory skin diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
