Abstract
Dendritic cells (DC) are a heterogeneous family of professional antigen-presenting cells classically recognized as most potent inducers of adaptive immune responses. In this respect, Langerhans cells have long been considered to be prototypic immunogenic DC in the skin. More recently this view has considerably changed. The generation of in vivo cell ablation and lineage tracing models revealed the complexity of the skin DC network and, in particular, established the existence of a number of phenotypically distinct Langerin+ and negative DC populations in the dermis. Moreover, by now we appreciate that DC also exert important regulatory functions and are required for the maintenance of tolerance toward harmless foreign and self-antigens. This review summarizes our current understanding of the skin-resident DC system in the mouse and discusses emerging concepts on the functional specialization of the different skin DC subsets in regulating T cell responses. Special consideration is given to antigen cross-presentation as well as immune reactions toward contact sensitizers, cutaneous pathogens, and tumors. These studies form the basis for the manipulation of the human counterparts of the murine DC subsets to promote immunity or tolerance for the treatment of human disease.
Highlights
The skin is the second largest barrier organ to the outside world besides the intestine
These findings suggested that Langerhans cells (LC) were not essential to induce the ear swelling reaction and that dermal Dendritic cells (DC) contributed to T cell activation in Contact hypersensitivity (CHS)
While the cells continuously probe their surroundings for invading pathogens, DC have to discriminate harmless from dangerous microbes, prevent inappropriate immune reactions against self-antigens, and limit collateral tissue damage once inflammation occurs during protective immune responses
Summary
The skin is the second largest barrier organ to the outside world besides the intestine. As such it is exposed to physical stress and to a wide variety of environmental antigens, including chemicals, commensal bacteria, and pathogens. The skin immune system must be prepared to detect and discriminate between these diverse antigens and subsequently induce appropriate tolerogenic or protective immune responses. To this aim, the skin contains a heterogeneous population of dendritic cells (DC, from Greek dendron “tree”) that represent key regulators of both innate and adaptive immune responses. As essential mediators of cutaneous immune reactions and homeostasis, considerable work has been focused to unravel the origins, phenotypic, and functional differences of the cells of the skin DC network [1,2,3]
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