Human dendritic cells — stars in the skin

Abstract

"A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells (DCs) are required to explain how this remarkable system is energized and directed." This is a quote by one of the greatest immunologists our community has ever known, and the father of dendritic cells, Ralph Steinman. Steinman's discovery of DCs in 1973 and his subsequent research opened a new field of study within immunology: DC biology and in particular the role of DCs in immune regulation in health and disease. Here, I review themes from our work and others on the complex network of dendritic cells in the skin and discuss the significance of skin DCs in understanding aspects of host defense against infections, the pathology of inflammatory skin diseases, and speculate on the future effective immunebased therapies. Keywords: Human dendritic cells r Skin r Vaccines A historical path to differentiating DC subsets in human skinHuman skin hosts several distinct DC subsets in two of its composed layers: Langerhans cells (LCs) in the epidermis and interstitial DCs in the dermis. LCs were identified in 1868 by Paul Langerhans as dendritic, nonpigmentary cells in the epidermis [1]. He speculated that these cells were acting as nervous system intraepidermal receptors for extracutaneous signals. The "branched skin cells resembling neuron", as he described them in his paper entitled "On the nerves of the human skin" [1]. Nestle and Nickoloff were the first to show that the dermis hosts multiple DC subsets, including CD1a + and CD14 + cells [2][3][4][5][6]. For many years, the painstaking task of isolating these distinct DC subsets in large numbers has made it difficult to study their biological functions. However, Jacques Banchereau and Christophe Caux discovered a way to differentiate large amounts of these cells in vitro from hematopoietic progenitor cells [7] and studies by Geissmann et al. established the generation of LC-like cells from human monocytes in the presence of . Interestingly, interaction of Correspondence: Dr. Eynav Klechevsky e-mail: eklechevsky@path.wustl.edu the latter with e-cadherin expressed by epidermal keratinocytes was required for a terminal differentiation of these cells into LCs [9]. These specialized culture systems, together with studies on DCs isolated from tissue samples, helped to unravel the complexity of the human skin DC system. Indeed, the DC system of the human skin has been evolutionarily shaped to answer to environmental challenges and coexist with an array of commensal bacteria that populate our skin. This is evident by the existence of several DC subsets, displaying distinctive phenotype and function (Fig. 1). Understanding the biology of DC subsets in humans with their unique specializations holds the potential of manipulating these cells and in doing so, discovering novel therapies for controlling human diseases. In particular, the induct...

A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease

“…Human skin is known to contain four distinct mDC subsets. Three of these, marked as CD1a + LCs are found in the epidermis (3,23). To define unique surface markers and to fully characterize expression patterns of each epidermal and dermal subset, we performed a flow cytometry analysis of 332 different surface proteins.…”

Eradication of damaged keratinocytes in cutaneous lichen planus forms demonstrated by evaluation of epidermal and follicular expression of CK15, indices of apoptosis and regulatory protein S100

“…LCs (Langerin+, CD1a+) constituting subsets of DCs populating epidermis have been explored extensively along with interstitial DCs, namely, resident dermal myeloid DCs (CD11c+, CD1c+), plasmacytoid blood DCs (BDCA-2+, CD123+), and a dermal population of CD14+ CD11c+ DCs found in normal skin, by other authors, who suggested that inflammatory skin diseases are characterized by a particular DC profile [70,71]. Over time, the spectra of effects of LCs on peripheral T cells, activation of skin resident memory T lymphocytes, a defense function against pathogens and tissue repair were explored [72,73]. In our study, immunohistochemical results of S100 staining observed in the case of classic LPP and LP, both intraepithelial LCs and dermal DCs, are consistent with the results of Santoro et al [49].…”

Human dendritic cell subsets and function in health and disease

“…DC can be found in lymphoid and nonlymphoid tissues, including blood, lymph nodes, tonsils, spleen, skin, liver, kidneys, lungs and gut [12,14,49,57,[60][61][62][63][64][65]. Transcriptome analysis demonstrates a clear relationship between CD1c ?…”