Moreover, dissection of the fate of human epidermal LCs after HSC transplantation revealed that 90% of LCs were of donor origin after 100 days (Collin et al., 2006). In contrast, cultured Langerhans cells produce IL-1β and IL-6. Michael R. Shurin, Anton A. Keskinov, in Encyclopedia of Immunobiology, 2016. Langerhans cells makes up 3–5% of the cells in the stratum spinosum [4]. Keratinocytes (KCs) are the major symbionts of LCs. There is a permanent cooperation between immune-related cells and cutaneous nerve fibers that release various neuropeptides affecting local immune activity [69]. However, upon culturing in vitro for 2–3 days, Langerhans cells upregulate MHC class II expression, as well as costimulatory molecules, and become functionally ‘mature’, i.e. Langerhans cells are immune cells that have an important role in the immune system. These results are consistent with recent data showing that IL-34 is the only Csf-1R ligand expressed in the epidermis of mice and humans, whereas both Csf-1 and IL-34 are produced in mouse and human dermis (Greter, Lelios, et al., 2012). Langerhans cell histiocytosis (LCH) is characterised by the proliferation of Langerhans cells in the skin, bones and bone marrow. Depending on the plane of sectioning, Birbeck granules appear as either rod-shaped (arrowheads) or tennis racket-shaped (stars) structures (original magnification × 40 000). KC-derived cytokines include interleukin (IL)-1, IL-6, IL-7, IL-8 and a steadily growing number of chemokines, IL-10, IL-12, IL-15, IL-18, granulocyte/macrophage colony-stimulating factor (GM-CSF), M-CSF, tumor necrosis factor (TNF) a as well as some of the factors regulating the growth of epithelial and/or mesenchymal cells, e.g., transforming growth factors (TGF) a and β, platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), as well as vascular endothelial growth factor (VEGF) (reviewed in Luger et al., 1996; Weninger et al., 1996). they become potent stimulators in mixed lymphocyte reactions. Langerhans cells are diffusely and strongly immunoreactive for CD1a (cytoplasmic). LCs cannot be easily identified on routine H&E sections. Interestingly, cytokines produced by surrounding cells (i.e. In normal numbers, they help fight infection. There also exist substantial numbers of dendritic leukocytes in the mammalian dermis. Many experts treat it as an autoimmune disorder. Thus, stealthy under barriers, LC and keratinocyte cooperate for LC to gain access to external Ags that have penetrated the SC barrier [71]. Langerhans weighed up arguments for LCs to be either cells of connective tissue or neural origin due to their striking dendritic morphology. Diagnostic Pathology: Head and Neck (Second Edition), Kelley's Textbook of Rheumatology (Ninth Edition), Development and Function of Myeloid Subsets, Czernielewski & Demarchez, 1987; Kanitakis, Morelon, Petruzzo, Badet, & Dubernard, 2011; Kanitakis, Petruzzo, & Dubernard, 2004, Frelinger, Hood, Hill, & Frelinger, 1979; Katz, Tamaki, & Sachs, 1979; Merad et al., 2002, Seneschal, Clark, Gehad, Baecher-Allan, & Kupper, 2012, Local Flaps in Facial Reconstruction (Second Edition), Lookingbill and Marks' Principles of Dermatology (Sixth Edition), Lookingbill and Marks' Principles of Dermatology (Fifth Edition), Kelley and Firestein's Textbook of Rheumatology (Tenth Edition), Anatomy, Physiology, Histology, and Immunohistochemistry of Human Skin, Skin Tissue Engineering and Regenerative Medicine, Paracortex region of lymph nodes (T cell-rich areas). dermal dendritic cells; DDCs), initiate immune responses that protect the integrity of this organ. In the epidermis, they are usually located at a suprabasal position and attach to neighboring keratinocytes via an E-cadherin- and Ca2+-dependent mechanism (Tang et al., 1993). Langerhans cells function as dendritic antigen-presenting cells, which migrate to the lymph nodes following stimulation in the epidermis. DDCs are located primarily in the perivascular areas of the superficial plexus. Depending on the plane of sectioning, Birbeck granules appear as either rod-shaped (arrowheads) or tennis racket-shaped (stars) structures (original magnification × 40 000). Human Langerhans cells within acetone-fixed epidermis stain with FITC-conjugated monoclonal antibody directed against CD1a. Langerhans cell histiocytosis (LCH) is a rare cancer that begins in LCH cells. LCs also exhibit membrane adenosine triphosphatase activity, contain vimentin-type intermediate filaments, express surface S-100 protein and CD34, and in normal epidermis (exception acrosyringeal keratinocytes) are the only cells that express Class II MHC Ags [11]. Systemic involvement has been noted in adults, particularly in the lungs. They originate from bone marrow precursors which, upon circulation in the peripheral blood, populate the skin. and, not determined; −, no expression; +/−, expression under certain conditions or in a subset of cells; +, low to moderate levels of expression; ++, moderate to high levels of expression. Cutaneous involvement is not necessarily a benign feature and many patients progress to multi-system disease. Langerhans cell aggregates are nodular, especially in the lungs, and are variably accompanied by eosinophils, foamy cells, neutrophils, and fibrosis. No difference in GVHD was found compared to controls when hLangerin-DTA mice were recipients in the C3H.SW → B6, CD8-dependent model or in the MHCII-mismatched B6bm12 → B6 model. 234, 120–141; Chapter 3 of Elder, D.E., Elenitsas, R., Johnson, Jr., B.L., Murphy, G.F., Xu, X., 2009. One of the pathways utilized by LCs to deliver antigen to T cells runs through langerin, which delivers antigen to Birbeck granules to be presented in a CD1a-restricted manner.7 The CD1 family of molecules is associated with presentation of glycolipids, and CD1a antigen presentation is independent of endosomal localization and acidification. In general, Langerhans cells in situ and freshly isolated Langerhans cells represent functionally ‘immature’ dendritic cells. In our study, LCH cells from bone/chronic lesions are undoubtedly immature Langerhans-type dendritic cells that express higher levels of CD68 and CD14 than normal LCs, intracellular MHC class II, are frequently negative for CD86 and DC-Lamp and have the same allostimulatory activity as immature normal DCs. PLATE 5.2. The functional role of epidermal LCs during immune responses to pathogens and peripheral tolerance varies with regard to the type of inflammatory signal and its localization. However, he remained cautious and considered the question of their nature as not definitely settled. There also exist substantial numbers of dendritic leukocytes in the mammalian dermis. LCH is a clonal neoplastic proliferation of Langerhans-type cells that express CD1a, langerin, and S100 protein, showing Birbeck granules by ultrastructural examination (Swerdlow, et al ,2008. CD205 is the essential molecule for antigen capturing and processing (Inaba et al., 1995; Jiang et al., 1995). LCs have also been shown to be capable of presenting nonpeptide antigens to CD1a-restricted T cells (Hunger et al., 2004).