In the skin and mucosa, DCs form a dense network of resident cells, both within pluri-stratified epithelia (epidermis, anogenital and oropharyngeal epithelium) as well as in subepithelial areas. The best-studied epithelial DC is the Langerhans cell (LC) of the epidermis. As described in Section 1.2, LCs are immature MDCs expressing CD1a, Lag-antigen, E-cadherin, and Birbeck granule-associated Ag langerin (Romani et al., 2003). LC activation induces their migration out of the epidermis, as it is observed in vivo in mouse studies (Baldwin et al., 2004; Ratzinger et al., 2002; Romani et al., 2003), ex vivo in cultures of human skin explants (Larsen et al., 1990; Schuler et al., 1993), and in situ in skin inflammatory diseases, where LC density is markedly decreased in areas of inflammation (Soumelis et al., 2002).
DCs in subepithelial areas, such as the dermis, have a phenotype of interstitial DCs (Shortman and Liu, 2002). In the mucosa of the intestinal tract, DCs are absent in the epithelium but are abundant in the subepithelial region. Here DCs are lined-up under the basal membrane and protrude thin dendrites through the epithelium into the intestinal lumen to sample for foreign Ag (Kelsall and Rescigno, 2004; Rescigno et al., 2001).
In contrast with these MDC subsets, pDCs are not resident cells of normal skin and mucosa (Gilliet et al., 2004; Wollenberg et al., 2002) but are present in HPV-related cervical cancer (Bontkes et al., 2005), skin melanoma lesions (Salio et al., 2003), lupus erythematosus (Farkas et al., 2001), psoriasis (Nestle et al., 2005), allergic contact dermatitis (Bangert et al., 2003) and in the nasal mucosa as early as 6 h after allergen challenge (Jahnsen et al., 2000), suggesting an active recruitment of blood pDCs to the site of peripheral inflammation. Furthermore, pDC recruitment to the skin has been observed in a therapeutic setting in which skin tumors were treated topically with TLR7 agonist imiquimod (Urosevic et al., 2005). As will be discussed further, pDC trafficking has many similarities with T cells, both being attracted to the site of inflammation by chemokines (SDF-1/CXCR3-ligands).
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