2002;27:474–82. Using an in vitro model, Lipsky et al. Learn vocabulary, terms, and more with flashcards, games, and other study tools. As shown in Table 2 , patients with SS-LCH account for the majority of LCH patients. See this image and copyright information in PMC. Sakata N, Toguchi N, Kimura M, Nakayama M, Kawa K, Takemura T. Development of Langerhans cell histiocytosis associated with chronic active Epstein-Barr virus infection. All authors read and approved the final manuscript. Matrix metalloproteinase-12 (MMP-12) in osteoclasts: new lesson on the involvement of MMPs in bone resorption. All patients, parents, control subjects, and physicians participated in the studies related to this review with consent to participate. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Langerhans cells (LC) are members of the dendritic cells family, residing in the basal and suprabasal layers of the epidermis and in the epithelia of the respiratory, digestive and urogenital tracts. In Knipe DM, Howley PM, editors. Our data from micro-dissected LC in both dermatopathic lymphadenopathy  and LCS  suggest that monocytes, precursor Langerhans cells, or Langerhans cells are one of the reservoir cells for MCPyV. Histiocytic disorders of children and adults: introduction to the problem, overview, historical perspective and epidemiology. 2001;25:630–6. However, recent studies indicate that LCH has a more neoplastic character [29,30,31]. Murakami I, Gogusev J, Fournet JC, Glorion C, Jaubert F. Detection of molecular cytogenetic aberrations in langerhans cell histiocytosis of bone. The numbers of MCPyV-DNA sequences in LCH tissues from patients younger than 2 years indicated a significant difference from tissues of non-LCH dermal disease patients of the same age . 1997;130:774–84.  demonstrated that IL-1 production and signaling from the IL-1 receptor are necessary components of Raf-induced transformation of NIH 3 T3 cells, which exclude other factors involvement in the vivo model . 2013;5:386–91. IL-1 and IL-6 stimulate IL-17 producing cells. Takayanagi H. New developments in osteoimmunology. Innate immune function between newborns and elderly is extremely different and large quantities of IL-6 after stimulation of receptors, such as TLR, by term newborns are indicated . We found IL-17A receptor expression levels in LCH cells are important for defining LCH subclasses. Med J Malaysia. Langerhans cells are dendritic but unpigmented and are found nearer the skin surface than melanocytes. 2008;50:924–7. Third, our results using LC/MS and LC/MRM-MS did not confirm the presence of IL-17A in LCH cells. We approached the IL-17A controversy and the IL-17A paradox from a new perspective, i.e. Am J Surg Pathol. This newer name emphasizes the histogenesis of the condition by specifying the type of lesional cell and removes the connotation of the unknown (\"X\") because its cellular basis has now been clarified. Similarly in cutaneous LCH, overreaction to stimuli such as a dermotropic MCPyV infection may occur . Coury et al. We think that balance between oncogene-induced senescence  and the requirement of IL-1 autocrine loop [2, 107, 108] of BRAF V600E mutation in pulmonary and non-pulmonary LCH indicates the clinical severity of the disease (Fig. Today, some LCS cases are considered as a malignant neoplasm initiated by MCPyV infection . BRAF mutation; ITIH4; Interleukin-1 loop model; Interleukin-17; Langerhans cell histiocytosis; Langerhans cell neoplasm; Langerhans cell sarcoma; Merkel cell polyomavirus; RAS/MAPK signaling pathway; Triple-factor model. https://doi.org/10.1186/s12964-018-0261-y, DOI: https://doi.org/10.1186/s12964-018-0261-y. Periodontal disease-Wikipedia. Yousem SA, Colby TV, Chen YY, Chen WG, Weiss LM. 2014;69:95–7. Chilosi M, Facchetti F, Calio A, Zamo A, Brunelli M, Martignoni G, Rossi A, Montagna L, Piccoli P, Dubini A, et al. Background: Akira S, Yamamoto M, Takeda K. Role of adapters in toll-like receptor signalling. DOI: 10.6014/jjomm.16.1 Corpus ID: 207848910. On the contrary, LCH is a reactive disorder with underlying neoplastic potential. Fettelschoss A, Kistowska M, LeibundGut-Landmann S, Beer HD, Johansen P, Senti G, Contassot E, Bachmann MF, French LE, Oxenius A, Kundig TM. Leahy MA, Krejci SM, Friednash M, Stockert SS, Wilson H, Huff JC, Weston WL, Brice SL. Erdem AP, Kasimoglu Y, Sepet E, Gencay K, Sahin S, Dervisoglu S. Oral manifestations may be the first sign of Langerhans cell histiocytosis. PLoS Med. One of the key cellular components with functional roles in both innate and adaptive arms of the immune response are Langerhans cells (LCs) (2). LCH is characterized by the proliferation of CD1a-positive activated Langerhans (not atypical Langerhans cell, morphologically)-like cells (LCH cells) generating inflammatory granuloma. On the contrary, LCH is a reactive disorder with underlying neoplastic potential. de Graaf JH, Tamminga RY, Dam-Meiring A, Kamps WA, Timens W. The presence of cytokines in Langerhans’ cell histiocytosis. Adolesc Med State Art Rev. 2010;16:685–7. 2008;14:81–7. Senechal B, Elain G, Jeziorski E, Grondin V, Patey-Mariaud de Serre N, Jaubert F, Beldjord K, Lellouch A, Glorion C, Zerah M, et al. Kanik A, Li M, Uramacher CD. 2012;24:141–9. PubMed 2005;17:1–14. Pediatr Pathol. d-Langerhans cell. showed high serum levels of IL-17A using the same enzyme-linked immunosorbent assay (ELISA) kit procedure in both: patients with LCH and controls without significant difference . In our analysis of LCH tissue, the results using LC/MS and LC/MRM-MS confirm the observation that the IL-17A reactivity in LCH cells observed by immunofluorescence  is due to nonspecific antibody binding as described by Allen et al. Pulmonary Langerhans’ cell histiocytosis: radiologic resolution following smoking cessation. We hypothesized that MCPyV infection triggered an IL-1 activation loop that lies beneath the pathogenesis of LCH and propose a new triple-factor model. CAS Triple-risk factor model is composed of three factors: cytogenetic abnormalities such as, Proposed reaction model in LCH activity. For example, scabies infections are reported to induce Langerhans cell hyperplasia, which mimics LCH . Eur J Intern Med. Weitzman S, Egeler RM. Langerhans cell histiocytosis (LCH) is a disorder that primarily affects children, but is also found in adults of all ages. 2009;15:483–4. Pancaldi et al. An endocrine model supported our data: the IL-17A serum levels and expression levels of IL-17A receptor are higher in LCH tissue in patients with LCH. In LCH, MCPyV infection may induce hyper-immunity in both LCH cells  and other inflammatory cells [11, 21]. Theill LE, Boyle WJ, Penninger JM. Its thickness varies according to the body site.The epidermis consists of stratified squamous epithelium. From study group: Any mnemonic for Hand Schuller Christian disease? Eur J Pediatr. In this regard, the recent discovery of MCPyV as a causal agent opened new therapeutic avenues for MCC . 2006;21:577–80. In addition, the serum sRANKL value is significantly higher in LCH patients than in the control group . Aliahmadi E, Gramlich R, Grutzkau A, Hitzler M, Kruger M, Baumgrass R, Schreiner M, Wittig B, Wanner R, Peiser M. TLR2-activated human langerhans cells promote Th17 polarization via IL-1beta, TGF-beta and IL-23. LCS is a malignant neoplasm initiated by MCPyV infection. Langerhans cells are present beyond the middle of the spinous epidermal layer , they have the capacity to capture external pathogens , and can act as antigen-presenting cells [10, 11]. Mechanistically, MCPyV-induced oncogenesis is considered to be induced by MCPyV large T (LT) antigen through molecular binding with the retinoblastoma protein . Cancer Res. We resolved this problem by adding data of IL-17A RECEPTOR mRNA expression uploaded by Allen et al. Langerhans cell histiocytosis reveals a new IL-17A-dependent pathway of dendritic cell fusion. NW, JN, MI, and MT participated in pathological analyses. In such conditions, tartrate-resistant acid phosphatase (osteoclast marker), vitronectin receptor, cathepsin K, and MMP9 are readily detected . white blood cells in the immune system that normally play an important role in protecting the body against viruses Virchows Arch. An oncogene-induced senescence is induced by cytogenetic abnormalities such as BRAF mutation and MEK mutation. Generally, no response is observed after secondary viral infection . Article 1987;7:569–74. Oral Health Prev Dent. 1987;1:208–9. Comparatively, LCS, distinct from the LCH, is a neoplastic lesion (or sarcoma) without presence of inflammatory granuloma frequently observed in the elderly. Those authors showed high serum IL-17A levels in LCH and argued that serum IL-17A supported healthy monocyte-derived dendritic cell (DC) fusion capacities in vitro, rather than serum IL-17A levels, which is more correlated with LCH severity (i.e., the IL-17A paradox) . Murakami I, Oh Y, Morimoto A, Sano H, Kanzaki S, Matsushita M, Iwasaki T, Kuwamoto S, Kato M, Nagata K, Hayashi K, Imashuku S, Gogusev J, Jaubert F, Oka T, Yoshino T. Clin Proteomics. The authors declare that they have no competing interests. Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S, Chang Y, Buck CB, Moore PS. Langerhans cells send out special agents — immune cells such as T cells and B cells — immediately after sensing any kind of danger in the skin. Raf-induced transformation requires an interleukin 1 autocrine loop. 2015 Feb 22;13:13. doi: 10.1186/s12964-015-0092-z. © 2021 BioMed Central Ltd unless otherwise stated. Article Studies and treatments focusing on these relationships have also been realized [131, 133, 134]. 2004;34:37–47. Barbey S, Gane P, Le Pelletier O, Nezelof C. Histiocytosis X Langerhans cells react with antiinterleukin-2 receptor monoclonal antibody. CAS Shimakage M, Sasagawa T, Kimura M, Shimakage T, Seto S, Kodama K, Sakamoto H. Expression of Epstein-Barr virus in Langerhans’ cell histiocytosis. Arch Dis Child. Medical definition of Merkel cell: a cell that occurs in the basal part of the epidermis, is characterized by dense granules in its cytoplasm, is closely associated with the unmyelinated tip of a nerve fiber, and probably functions in tactile sensory perception. b-Lymphocyte. Mol Cell Biochem. Thus, we suggest that MCPyV may play specific role as an oncogenic factor in certain subtypes of LCS. Langerhans cells (LCs) are epidermal immune cells of myeloid origin. In particular, the receptor activator of nuclear factor kappa-B ligand (RANKL) is regarded as the most important protein . A mutation in POLR3E impairs antiviral immune response and RNA polymerase III. In the future, stimuli that govern IL-17A or IL-17A receptor production might serve as therapeutic targets to stop LCH progression, similar to cessation of smoking which induces pulmonary LCH regression [11, 68], which is almost always a disease of smokers . Lancet. Nat Rev Immunol. KH, TY, SI, and FJ supervised the project. We previously proposed that external pathogens may be initially recognized by Langerhans cells and may subsequently infect Merkel cells which are mostly located at the basal cell layer of the epidermis (Fig. da Costa CE, Annels NE, Egeler RM. However, there are no specific pathological definitions between the LCH subtypes such as self-healing SS-LCH, LCH-RO (−), and life-threatening LCH-RO (+). The latter form is frequent in children younger than 2 years, whereas SS-LCH is more common in children older than 2 years [11, 15]. 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