Antigen families

The ability to migrate is a central feature of DCs and indispensable for their functions within the immune system (1). Studies on the migratory properties of DCs provide highly valuable information about their biology. DCs reside in an immature state in peripheral tissues where they act as sentinels to induce protective immunity against incoming danger or immune tolerance to maintain homeostasis to self antigens. In the steady-state, heterogeneous populations of DCs  are localized in distinct anatomic sites (eg skin) according to their unique homing properties. In the absence of danger, tissue-resident DCs emigrate via afferent lymph towards draining lymph nodes, presumably to instruct T cell tolerance (2). Inflammatory conditions result in an important mobilization of blood DC precursors into sites of tissue injury. Illustrating the plasticity of the DC system, conventional DCs are recruited in part from inflammatory monocytes (3).
Trafficking directly from blood to lymph nodes via high endothelial venules, plasmacytoid DCs (pDCs) are normally absent from peripheral tissues (4). However, pDCs may be recruited to inflammatory sites under pathological conditions.
It was realized early on that activation (eg by LPS or pro-inflammatory cytokines) of resident or newly-recruited conventional DCs at inflammatory sites results in their rapid egress into afferent lymphatics. After crosstalk with the lymphatic vessels (5) such DCs reach the draining lymph nodes in a fully-mature state with optimal capacity for both antigen-presentation and T cell activation. Several mechanisms are responsible for the distinct migration patterns of DCs observed in the steady-state and in perturbed tissues. First, DCs respond to a variety of chemokines, a family of secreted chemotactic factors that guide the navigation of various types of leukocytes (6).
Immature DCs express many receptors for “inflammatory” chemokines such as MIP-3α/CCL20 (mAb DENDRITICS: DDX0420, DDX0430, DDX0431) produced by epithelial cells (eg epidermal keratinocytes) (7). MIP-3α/CCL20 (mAb DENDRITICS: DDX0420, DDX0430, DDX0431) and its receptor CCR6 are important components for the recruitment of Langerhans cells, and consistently are strongly up-regulated in inflammatory skin disorders, eg in psoriasis (8). Activation of DCs under pro-inflammatory conditions induces a change in their profile of chemokine receptors. This modification allows for enhanced trafficking of DCs from inflamed tissues towards draining lymph nodes, a process in which the chemokine receptor CCR7 plays a critical role (9).
In addition to the chemokines, several other mechanisms control the migration of DCs. These include non-chemokine chemotactic factors such as formylated peptides (fMLP) or the antimicrobial defensins. In addition, several non-chemotactic molecules promote or inhibit DC migration. Finally, physical barriers must be crossed by migrating DCs. Matrix metalloproteinases (MMPs) play an essential role in the degradation of such obstacles. MMP12 (mAb DENDRITICS) is expressed by Langerhans cells, and strikingily abundant in Langerhans cell histiocytosis, a malignancy in which this protease may play an important role (10). Further understanding the patterns and mechanisms of DC migration will undoubtedly open new avenues for therapeutic translation.

References
1. Cavanagh LL, Von Andrian UH.. Travellers in many guises: the origins and destinations of dendritic cells», 2002 Immunol Cell Biol 80: 448-462
2.Steinman RM, Hawiger D, Nussenzweig MC, Tolerogenic dendritic cells, 2003 Annu Rev Immunol 21: 685-711
3.Geissmann F, Jung S, Littman DR.. Blood monocytes consist of two principal subsets with distinct migratory properties 2003 Immunity 19: 71-8
4.Colonna M, Trinchieri G, Liu YJ.. Plasmacytoid dendritic cells in immunity, 2004 Nat Immunol 5: 1219-1226
5.Randolph GJ, Angeli V, Swartz MA.. Dendritic-cell trafficking to lymph nodes through lymphatic vessels, 2005 Nat Rev Immunol 5: 617-628
6.Bendall L.. Chemokines and their receptors in disease, 2005 Histol Histopathol 20: 907-926
7.Dieu-Nosjean MC, Massacrier C, Homey B, Vanbervliet B, Pin JJ, Vicari A, Lebecque S, Dezutter-Dambuyant C, Schmitt D, Zlotnik A, Caux C., Macrophage inflammatory protein 3alpha is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors, 2000 J Exp Med 192: 705-18
8.Homey B, Dieu-Nosjean MC, Wiesenborn A, Massacrier C, Pin JJ, Oldham E, Catron D, Buchanan ME, Muller A, deWaal Malefyt R, Deng G, Orozco R, Ruzicka T, Lehmann P, Lebecque S, Caux C, Zlotnik A.. Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis 2000 J Immunol 164: 6621-6632
9.Ohl L, Mohaupt M, Czeloth N, Hintzen G, Kiafard Z, Zwirner J, Blankenstein T, Henning G, Forster R.. CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions, 2004 Immunity 21: 279-288
10. Rust R, Kluiver J, Visser L, Harms G, Blokzijl T, Kamps W, Poppema S, van den Berg A.. Gene expression analysis of dendritic/Langerhans cells and Langerhans cell histiocytosis, 2006 J Pathol, May 23