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Langerhans dendritic cells

Tingting Zheng, Weiheng Zhao, Hongjin Li, Shuxiu Xiao, Ran Hu, Miaomiao Han, Heng Liu, Yeqiang Liu, Kinya Otsu, Xinguang Liu, Gonghua Huang
Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiform skin inflammation, we found that p38α activity in Langerhans cells (LCs), a skin-resident subset of DCs, promoted the generation of T cells that produce IL-17, a proinflammatory cytokine that is implicated in autoimmune disease. Deletion of p38α in LCs, but not in other skin or circulating DC subsets or T cells, decreased T cell-mediated psoriasiform skin inflammation in mice. The activity of p38α in LCs specifically promoted IL-17 production from γδ and CD4+ T cells by increasing the abundance of IL-23 and IL-6, two cytokines that stimulate IL-17 secretion...
March 13, 2018: Science Signaling
Benjamin H Durham
The systemic histiocytoses encompass a clinically heterogeneous group of disorders leading to tissue damage secondary to the accumulation and infiltration of pathological cells thought to be derived from the dendritic or monocytic lineages with accompanying inflammation. For decades, whether or not the histiocytoses were inflammatory or neoplastic disorders was unclear, and their cellular origins have long been obscure and heavily debated. However, the rise of the molecular era led to the discovery of recurrent BRAFV600E mutations in approximately 50% of patients with Langerhans cell and non-Langerhans cell histiocytoses, which provided the first convincing evidence that these are indeed histiocytic neoplasms...
March 8, 2018: Seminars in Cell & Developmental Biology
Noah A Brown, Kojo S J Elenitoba-Johnson
PURPOSE OF REVIEW: Langerhans cell histiocytosis (LCH) is a neoplasm of dendritic cells with a wide clinical spectrum. Localized pulmonary LCH occurs in young adults with a history of smoking and can either resolve spontaneously or lead to progressive decline in pulmonary function. Young children can also present with localized disease - frequently bone or skin - or with multifocal or multisystem disease. Clinical outcomes in these patients also vary widely, ranging from spontaneous resolution to multiorgan failure and death...
February 20, 2018: Current Opinion in Pulmonary Medicine
S Wagner, H Böckmann, S Gattenlöhner, J P Klussmann, C Wittekindt
Based on clinical and experimental data, oropharyngeal squamous cell carcinomas (OPSCC) associated with human papillomavirus (HPV) have been recognized as a distinct entity of head and neck cancers. However, outside of clinical trials, HPV status currently has no impact on treatment. The natural replication cycle of HPV takes place in epithelial cells, and is thus spatially separated from cytotoxic immune cells in the epidermis. Dendritic cells (Langerhans cells, LC), however, are frequent in this upper dermal layer...
February 15, 2018: HNO
Maria Papadopoulou, Paraskevi Panagopoulou, Anastasia Papadopoulou, Emmanuel Hatzipantelis, Ioannis Efstratiou, Assimina Galli-Tsinopoulou, Efimia Papadopoulou-Alataki
Langerhans cell histiocytosis (LCH) is a rare hematologic disorder that results from the clonal multiplication and accumulation of immature dendritic Langerhans cells. Its reported incidence rate varies, but is considered to be 2.6-8.9 per million children who are <15 years of age each year. It may affect any system or organ. The present study reported 4 pediatric LCH cases in order to highlight the heterogeneity of the initial presentation, and the pitfalls that may mislead clinicians and delay diagnosis...
March 2018: Molecular and Clinical Oncology
Julie Deckers, Hamida Hammad, Esther Hoste
In the last few decades, our understanding of Langerhans cells (LCs) has drastically changed based on novel findings regarding the developmental origin and biological functions of these epidermis-specific resident immune cells. It has become clear that LCs not only exert pivotal roles in immune surveillance and homeostasis but also impact on pathology by either inducing tolerance or mediating inflammation. Their unique capabilities to self-renew within the epidermis, while also being able to migrate to lymph nodes in order to present antigen, place LCs in a key position to sample the local environment and decide on the appropriate cutaneous immune response...
2018: Frontiers in Immunology
Herbert Strobl, Corinna Krump, Izabela Borek
Human Langerhans cells (LC) can be generated ex vivo from hematopoietic precursor cells in response to cytokines and cell-membrane associated ligands. These in vitro differentiation models provided mechanistic insights into the molecular and cellular pathways underlying the development of this unique, epithelia-associated dendritic cell subset. Notably, the human epidermal microenvironment is fully sufficient to induce LC differentiation from hematopoietic progenitors. Hence, dissecting the molecular characteristics of the human epithelial/epidermal LC niche, and testing defined ligands for their capacity to induce LC differentiation, led to a refined molecular model of LC lineage commitment...
February 12, 2018: Seminars in Cell & Developmental Biology
Yufeng Wang, Shu Shang, Qianqian Sun, Junjun Chen, Guanhuan Du, Hong Nie, Xiaozhe Han, Guoyao Tang
OBJECTIVE: Investigation of dendritic cell (DC) subsets and expression patterns of Toll-like receptors (TLRs) was conducted to understand the pathogenesis in oral lichen planus (OLP). STUDY DESIGN: Blood, OLP lesion, and control samples were collected. Four DC subsets (CD11c + CD123 - myeloid DC1 [mDC1], CD141 + mDC2, CD11c - CD123 + plasmacytoid DC [pDC], and CD1a + CD207 + Langerhans cells [LC]) were investigated via flow cytometry (FCM) and immunohistochemical staining...
December 18, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Maria Gschwandtner, Philip Kienzl, Poojabahen Tajpara, Christopher Schuster, Gernot Stipek, Maria Buchberger, Michael Mildner, Mario Mairhofer, Wolfgang Eppel, Martin Vierhapper, Johannes Pammer, Rupert Koller, Adelheid Elbe-Bürger, Erwin Tschachler
RTN1 is an endoplasmic reticulum-associated protein that has initially been identified in neuronal tissues. Here we show that the main isoform RTN1A is a marker for dendritic cells. In the skin HLA-DR+CD1ahighCD207+CD11cweak Langerhans cells were the only cells in the epidermis and HLA-DR+CD11c+ dendritic cells were the main cells in the dermis expressing this protein. RTN1A+ dendritic cells were also demonstrated in gingiva, trachea, tonsil, thymus and peripheral blood. During differentiation of MUTZ-3 cells into Langerhans cells, expression of RTN1A mRNA and protein preceded established Langerhans cell markers CD1a and CD207, and RTN1A protein partially co-localized with the endoplasmic reticulum marker protein disulfide isomerase...
January 21, 2018: Journal of Investigative Dermatology
Xilin Zhang, Yi Yao, Wei-Zen Wei, Zeng-Quan Yang, Jun Gu, Li Zhou
TGF-β-inducible early gene 1 (TIEG1), also known as Krüppel-like factor 10 (Klf10), represents a major downstream transcription factor of transforming growth factor-β1 (TGF-β1) signaling. Epidermal Langerhans cells (LCs), a unique subpopulation of dendritic cells (DC), essentially mediates immune surveillance and tolerance. TGF-β1 plays a pivotal role in LC maintenance and function after birth, although the underpinning mechanisms remain elusive. Here, we hypothesized that TIEG1 might be involved in TGF-β1-mediated LC homeostasis and function...
December 22, 2017: Oncotarget
Tal Capucha, Noam Koren, Maria Nassar, Oded Heyman, Tsipora Nir, Maayan Levy, Gili Zilberman-Schapira, Katya Zelentova, Luba Eli-Berchoer, Martin Zenke, Thomas Hieronymus, Asaf Wilensky, Herve Bercovier, Eran Elinav, Björn E Clausen, Avi-Hai Hovav
Mucosal Langerhans cells (LCs) originate from pre-dendritic cells and monocytes. However, the mechanisms involved in their in situ development remain unclear. Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium, TGF-β1 finalizes LC differentiation, and ALK5 is crucial to this process. Moreover, the local microbiota has a major impact on the development of mucosal LCs, whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction...
January 17, 2018: Journal of Experimental Medicine
C M Luder, T M Nordmann, E Ramelyte, B Mühleisen, K Kerl, O Boyman, E Guenova, R Dummer
Histiocytoses are rare disorders characterized by the accumulation of cells derived from macrophages, dendritic cells, or monocytes in various tissues. There is a broad spectrum of disease manifestations with some subtypes commonly showing skin lesions while in others the skin is rarely involved. Here we describe cutaneous manifestations of histiocytoses belonging to the Langerhans group (L group), the group of cutaneous and mucocutaneous histiocytoses (C group) and the group of Rosai-Dorfman disease and related histiocytoses (R group) according to the current classification...
January 16, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Nicole Kuhlmann, Lena Heinbockel, Wilmar Correa, Thomas Gutsmann, Torsten Goldmann, Uwe Englisch, Klaus Brandenburg
In previous years, we developed anti-infective drugs based on antimicrobial peptides (AMPs), which have been shown to effectively block severe infections and inflammation in vitro as well as in vivo. Besides systemic application, the occurrence of severe local infections necessitates a topical application for example in the case of severe skin and soft tissue infections (SSTI). Recent investigations show that the synthetic anti-lipopolysaccharide peptide (SALP) Pep19-2.5 (Aspidasept® I) and a variant called Pep19-4LF (Aspidasept® II) are able to supress inflammation reactions also in keratinocytes, Langerhans cells, and dendritic cells from the skin...
January 11, 2018: European Journal of Pharmaceutical Sciences
Xuejun Tian, Jie Xu, Christopher Fletcher, Jason L Hornick, David M Dorfman
EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. We found that the majority of cases of histiocytic and dendritic cell neoplasms, including histiocytic sarcoma, follicular dendritic cell sarcoma, Langerhans cell histiocytosis, and interdigitating dendritic cell sarcoma, show strong EZH2 expression by immunohistochemical staining, in contrast to benign histiocytic lesions and normal cellular counterparts, which did not show EZH2 expression, suggesting that this molecule may function as an oncogenic protein in these neoplasms...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Tae-Gyun Kim, Sung Hee Kim, Min-Geol Lee
Dendritic cells (DCs) are heterogeneous groups of innate immune cells, which orchestrate immune responses by presenting antigens to cognate T cells and stimulating other types of immune cells. Although the term 'DCs' generally represent highly mixed subsets with functional heterogeneity, the classical definition of DCs usually denotes conventional DCs (cDCs). Skin contains a unique DC network mainly composed of embryo precursor-derived epidermal Langerhans cells (LCs) and bone marrow-derived dermal cDCs, which can be further classified into type 1 (cDC1) and type 2 (cDC2) subsets...
December 23, 2017: International Journal of Molecular Sciences
Kalum Clayton, Andres F Vallejo, James Davies, Sofia Sirvent, Marta E Polak
Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels. These cells determine the appropriate adaptive immune response (inflammation or tolerance) by interpreting the microenvironmental context in which they encounter foreign substances. In a normal physiological, "non-dangerous" situation, LCs coordinate a continuous state of immune tolerance, preventing unnecessary and harmful immune activation. Conversely, when they sense a danger signal, for example during infection or when the physical integrity of skin has been compromised as a result of a trauma, they instruct T lymphocytes of the adaptive immune system to mount efficient effector responses...
2017: Frontiers in Immunology
Joji Shimono, Hiroaki Miyoshi, Fumiko Arakawa, Kensaku Sato, Takuya Furuta, Reiji Muto, Eriko Yanagida, Yuya Sasaki, Daisuke Kurita, Keisuke Kawamoto, Koji Nagafuji, Koichi Ohshima
Histiocytic and dendritic cell neoplasms are rare and poorly studied. We report the clinical characteristics and prognostic factors in such cases in Japan. We investigated the clinical characteristics and survival in 87 adult patients with histiocytic and dendritic cell neoplasms. Fifty patients had histiocytic sarcoma, 12 had Langerhans cell histiocytosis, 11 had follicular dendritic cell sarcoma, 8 had Langerhans cell sarcoma, 6 had interdigitating cell sarcoma and 1 had indeterminate dendritic cell sarcoma...
November 17, 2017: Oncotarget
L H Eaton, K T Mellody, S M Pilkington, R J Dearman, I Kimber, C E M Griffiths
Psoriasis is a common skin condition driven by increased expression of interleukin (IL)-17. Langerhans' cells (LC) are epidermal dendritic cells that regulate cutaneous immune responses. Within uninvolved skin of patients with psoriasis, LC display impaired migration from the epidermis. Here the role of keratinocytes (KC) in the regulation of LC function, and the response of KC to IL-17 has been investigated. Keratinocytes were cultured from the uninvolved skin of psoriasis patients and healthy individuals with or without IL-17 treatment and the conditioned medium examined for its ability to alter LC function in an ex vivo human skin explant model...
December 1, 2017: British Journal of Dermatology
Narmadha Subramanian, Zeguang Wu, Frank Reister, Kerstin Laib Sampaio, Giada Frascaroli, Luka Cicin-Sain, Thomas Mertens
Apart from classical antigen-presenting cells (APCs) like dendritic cells and macrophages, there are semiprofessional APCs such as endothelial cells (ECs) and Langerhans' cells. Human cytomegalovirus (HCMV) infects a wide range of cell types including the ECs which are involved in the trafficking and homing of T cells. By investigating the interaction of naïve T cells obtained from HCMV-seronegative umbilical cord blood with autologous HCMV-infected human umbilical vein ECs (HUVECs), we could show that the activation of naïve T cells occurred after 1 day of peripheral blood mononuclear cell (PBMC) exposure to HCMV-infected HUVECs...
November 21, 2017: Journal of General Virology
Paul G Whitney, Christina Makhlouf, Beth MacLeod, Joel Z Ma, Elise Gressier, Marie Greyer, Katharina Hochheiser, Annabell Bachem, Ali Zaid, David Voehringer, William R Heath, Mayura V Wagle, Ian Parish, Tiffany A Russell, Stewart A Smith, David C Tscharke, Thomas Gebhardt, Sammy Bedoui
Resolution of virus infections depends on the priming of virus-specific CD8(+) T cells by dendritic cells (DC). While this process requires MHC class I-restricted antigen presentation by DC, the relative contribution to CD8(+) T cell priming by infected DC is less clear. We have addressed this question in the context of a peripheral infection with herpes simplex virus type 1 (HSV). Assessing the endogenous, polyclonal HSV-specific CD8(+) T cell response, we found that effective in vivo T cell priming depended on the presence of DC subsets specialized in cross-presentation while Langerhans cells and plasmacytoid DC were dispensable...
November 15, 2017: Journal of Virology
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