Functional Specialization of Skin Dendritic Cell Subsets in Regulating T Cell Responses

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.

A Key Role for Inhibins in Dendritic Cell Maturation and Function

“…Under inflammatory conditions, LC increase MHCII and co-stimulatory molecules and, in parallel, lose their extended phenotype and acquire a round shape, that allows them to migrate to LN. These changes are accompanied by down regulation of E-cadherin and up-regulation of N-cadherin and CCR7 (reviewed in [45]). Interestingly, upregulation of costimulatory markers on LC was impaired after in vivo LPS stimulation in Inhα -/- mice, which correlates with the in vitro results of BMDC maturation.…”

“…In DTH assays, both LC and dermal DCs are important to induce a T cell response [45]. The Inhα -/- mice showed poor DTH in response to OVA challenge, which could be the result of a decreased maturation and consequently reduced migration of CD8 - CD207 + DCs to the dLN.…”

mRNA vaccines — a new era in vaccinology

“…A variety of antigen-presenting cells reside in the skin 149 , making it an ideal site for immunogen delivery during vaccination (FIG. 3).…”

Interplay of innate and adaptive immunity in metal-induced hypersensitivity

“…DCs that reside in the skin include Langerhans cells in the epidermis and two subsets of dermal DCs, langerin + dermal DCs and langerin neg dermal DCs (Figure 2) [25]. Migration of DCs from the skin to the draining LNs is required for sensitization with other peripheral antigens including small molecule contact sensitizers [26].…”