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Diseases of Infancy and Childhood
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Diagnosis is dependent on clinical and histologic findings. Histology can show infiltration of typical Langerhans cells (confirmable by positive CDla, S100, or langerin immunostaining). The differential diagnosis includes seborrheic dermatitis, candidal diaper dermatitis, atopic dermatitis, scabies, psoriasis, and mastocytosis.
Viral infections
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Sarah Elizabeth Blutt, Mary K. Estes, Satya Dandekar, Phillip D. Smith
The ability of Langerhans cells in the vaginal epithelium to capture and internalize HIV-1 has been conclusively demonstrated by electron microscopy. Langerhans cells are present in the upper layers of the epithelium and may extend processes between epithelial cells into the apical surface of the epithelium, positioning the cells to capture and internalize HIV-1 inoculated onto the mucosal surface (Figure 28.5). Langerhans cells express CD207 (langerin, a C-type lectin) and CD4 and CC-chemokine 5 (CCR5), the HIV-1 primary receptor and coreceptor, but blocking studies suggest that only CD4 and CCR5 are involved in HIV-1 endocytosis. Once captured, HIV-1-containing Langerhans cells can exit the upper epithelium in an ex vivo tissue system in which the underlying stroma has been removed. However, Langerhans cells do not migrate through explanted vaginal mucosa in which the subjacent stroma remains attached to the epithelium, and Langerhans cells have not been identified in the draining lymph nodes. Moreover, langerin, at least on skin Langerhans cells, mediates the binding and internalization of HIV-1 into Birbeck granules, which degrade the virus. Thus, dermal Langerhans cells inhibit T-cell infection by viral clearance through langerin-mediated internalization, but whether vaginal Langerhans cells also serve as a barrier to HIV-1 infection is unclear.
Immunology
Published in M. Alan Menter, Caitriona Ryan, Psoriasis, 2017
Langerhans cells are a type of immature conventional DC that reside in the epidermis.7 They are actively phagocytic and contain large granules known as Birbeck granules. CD1a and langerin (CD207) are used as specific markers to distinguish Langerhans cells from other DC subsets. The main role of Langerhans cells is to take up and process antigens and migrate to local skin-draining lymph nodes where they present to antigen-specific T cells.2 However, the role of Langerhans cells in psoriasis immunopathogenesis is still unclear.3 Recently, attention has focused on the potential importance of Langerhans cells in uninvolved skin sites of psoriasis patients, and it has been demonstrated that Langerhans cell migration is impaired in early onset psoriasis (onset before 40 years of age).31,32 Also, the treatment with TNF-α inhibitors (adalimumab, etanercept) and anti-IL-12p40 antibody (ustekinumab) significantly restored epidermal Langerhans cell migration in uninvolved skin.33 Although the influence of impaired Langerhans cell mobilization on the pathogenesis of psoriasis is uncertain, the loss of Langerhans cell motility may have an impact on the ability of these cells to sense the local antigenic microenvironment and regulate cutaneous immune responses.
Dendritic Cells Currently under the Spotlight; Classification and Subset Based upon New Markers
Published in Immunological Investigations, 2021
Samaneh Soltani, Mahdi Mahmoudi, Elham Farhadi
Pre-cDC2 committed to the cDC2 subset, which is defined by the surface expression of CD1 c (Breton et al. 2016). IRF4 is considered as the differential transcription factor for cDC2, albeit it is clear that additional TFs exist, e.g., ID2, ZEB2, Neurogenic locus notch homolog protein 2 (Notch2)/KLF4 (Collin and Bigley 2018; Obregon et al. 2017; Schultze and Aschenbrenner 2019). CD1 c+ DCs express a wide repertoire of TLRs, including TLR1, TLR2, TLR4, TLR5, TLR6, and TLR8 (Collin and Bigley 2018). Human cDC2 subset can be detected in lymphoid and non-lymphoid tissues, including blood, LNs, tonsils, spleen, skin, liver, kidneys, lungs, and gut. Human CD1 c+ DCs are the most frequent cDC subset found in blood, whereas CD141+ DCs form a minute blood population (Merad et al. 2013). In human tissues, TGF-β induces the expression of Langerin (CD207) on cDC2 cells (O’Keeffe et al. 2015). In the skin, cDC2 s express more CD11c, CD11b, and lower CD1a, Langerin, and Epithelial cell adhesion molecule (EpCAM) compared to Langerhans cells (Bigley et al. 2015; De Monte et al. 2016). Langerin is one of the markers that differ between human and mice, that is mean, in human’s tissues cDC2 spontaneously present low langerin, in contrast to the mouse in which cDC1 express langerin (Collin and Bigley 2018).
Adult Langerhans cell histiocytosis of the central nervous system
Published in Baylor University Medical Center Proceedings, 2020
Walter R. Duarte-Celada, Smathorn Thakolwiboon, Luis Brandi, Christopher Duarte-Celada, Mirla Avila
Langerhans cell histiocytosis (LCH) is a disorder characterized by aberrant function and proliferation of Langerhans cells,1 a unique dendritic cell subset found in the epidermis, squamous mucosa, and lymphoid organs. Langerhans cells express CD68, CD1a, and Langerin.1,2 Adult-onset LCH is extremely rare, with an estimated incidence of 0.07 cases per million.3 The etiology of LCH is not completely understood, but the oncogenic BRAF V600E mutation has been identified in up to 57% of cases. This finding supports a neoplastic origin.4 BRAF mutation keeps the MAPK pathway constitutively active (gene expression, cellular growth, survival).1 Central nervous system (CNS) involvement is relatively rare in LCH. It can manifest with a large variety of symptoms, making the diagnosis complex.
Novel approaches to glycomimetic design: development of small molecular weight lectin antagonists
Published in Expert Opinion on Drug Discovery, 2021
Vishnu C. Damalanka, Amarendar Reddy Maddirala, James W. Janetka
In order to achieve good affinity for DC-SIGN, multivalent analogs have been developed as the first antagonists for DC-SIGN such as those reported by Delgado and Rojo groups in 2003, one with an IC50 value of 337 nM in preventing EBOV infection [167]. Following the same convergent approach, the Moravcova group developed nonavalent and dodecavalent mannopyranose-dendrimers with IC50 values of 128 µM and 67 µM (compounds 42 and 43, Table 10), respectively, with a 420-fold increase in potency compared to fucosides [168]. However, these ligands also bind langerin due to its identical carbohydrate-binding specificity, thus causing a concern about potential toxicity. In addition, oligosaccharides and multivalent glycodendrimers are easily metabolized, are highly polar, and have no or only limited oral bioavailability. Considering these impediments, Bernardi and Fieschi groups reported pseudo disaccharide-based analogs as novel ligands for DC-SIGN like 44 (Table 10) which has good selectivity over langerin [169] (DC-SIGN and langerin with IC50 values 956 µM and 1474 µM) but low binding affinity relative to 42 and 43. To improve the selectivity toward DC-SIGN the methyl ester groups of the cyclohexane moiety were replaced with amides as in compound 45 [DC-SIGN (IC50 = 329 µM) vs langerin (IC50 = 2556 µM)]. Another analog 46, designed by modification of mannose ring at the 6 position [169], encompassed the best affinity and selectivity for DC-SIGN (IC50 = 254 µM) versus langerin (IC50 > 4400 µM). Non-carbohydrate ligands of DC-SIGN were recently discovered by fragment-based screening that have µM affinity by SPR but do not bind to the sugar pocket but bind to one of the five identified allosteric pockets with affect Ca2+ binding [170].