Search results for "Langerhans Cells"

E-Cadherin is Dispensable to Maintain Langerhans Cells in the Epidermis.

2019

The cell adhesion molecule E-cadherin is a major component of adherens junctions and marks Langerhans cells (LC), the only dendritic cell (DC) population of the epidermis. LC form a dense network and attach themselves to the surrounding keratinocytes via homophilic E-cadherin binding. LC activation, mobilization, and migration require a reduction in LC E-cadherin expression. To determine whether E-cadherin plays a role in regulating LC homeostasis and function, we generated CD11c-specific E-cadherin knockout mice (CD11c-Ecaddel). In the absence of E-cadherin−mediated cell adhesion, LC numbers remained stable and similar as in control mice, even in aged animals. Intriguingly, E-cadherin−defi…

Dermal CD207-Negative Migratory Dendritic Cells Are Fully Competent to Prime Protective, Skin Homing Cytotoxic T-Lymphocyte Responses

2018

Dendritic cells (DCs) are important inducers and regulators of T-cell responses. They are able to activate and modulate the differentiation of CD4+ and CD8+ T cells. In the skin, there are at least five phenotypically distinct DC subpopulations that can be distinguished by differential expression of the cell surface markers CD207, CD103, and CD11b. Previous studies have suggested that dermal CD11b−CD207+ conventional type 1 DCs are indispensable for the priming of a skin homing cytotoxic T-lymphocyte response. However, conventional type 1 DCs are also the only skin DC subset capable of cross-presenting exogenous antigens on major histocompatibility complex class I. Thus, it remained unclear…

Selective AhR knockout in langerin-expressing cells abates Langerhans cells and polarizes Th2/Tr1 in epicutaneous protein sensitization

2020

The aryl hydrocarbon receptor (AhR) represents an environmental sensor regulating immune responses. In the skin, AhR is expressed in several cell types, including keratinocytes, epidermal Langerhans cells (LC), and dermal dendritic cells (DC). The mechanisms how AhR activates or inhibits cutaneous immune responses remain controversial, owing to differences in the cell-specific functions of AhR and the different activating ligands. Therefore, we sought to investigate the role of AhR in LC and langerin(+) and negative DC in the skin. To this aim, we generated Langerin-specific and CD11c-specific knockout ((−/−)) mice lacking AhR, respectively, in LC and Langerin(+) dermal DC and in all CD11c(…

In cutaneous leishmaniasis, induction of retinoic acid in skin-derived Langerhans cells is not sufficient for induction of parasite persistence-media…

2017

Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation

2016

Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-…

Solid nanoemulsion as antigen and immunopotentiator carrier for transcutaneous immunization

2015

Imiquimod, a toll-like receptor 7 (TLR7) agonist, is an active pharmaceutical ingredient (API) established for the topical treatment of several dermal cancerous and precancerous skin lesions. Within this work, the immunostimulatory effect of imiquimod is further exploited in a transcutaneous immunization (TCI) approach based on a solid nanoemulsion (SN) formulation. SN contains a combination of imiquimod with the model peptide antigen SIINFEKL as a novel approach to omit needle and syringe and optimize dermal antigen administration. Excipients including sucrose fatty acid esters and the pharmaceutically acceptable oils MCT (middle chain triglycerides), avocado oil, jojoba wax and squalene a…

Transcutaneous immunization with a novel imiquimod nanoemulsion induces superior T cell responses and virus protection

2017

Abstract Background Transcutaneous immunization (TCI) is a novel vaccination strategy utilizing the skin associated lymphatic tissue to induce immune responses. TCI using a cytotoxic T lymphocyte (CTL) epitope and the Toll-like receptor 7 (TLR7) agonist imiquimod mounts strong CTL responses by activation and maturation of skin-derived dendritic cells (DCs) and their migration to lymph nodes. However, TCI based on the commercial formulation Aldara only induces transient CTL responses that needs further improvement for the induction of durable therapeutic immune responses. Objective Therefore we aimed to develop a novel imiquimod solid nanoemulsion (IMI-Sol) for TCI with superior vaccination …

Modification of Peripheral Blood T-Lymphocyte Surface Receptors and Langerhans Cell Numbers in Hereditary Angioedema

1986

Hereditary angioedema (HAE) is a disease related to a complement disorder, namely a deficiency of C1 esterase inhibitor. Complement-split products are implicated in the regulation of the immune response, and we have compared some immunologic parameters between HAE and normal individuals. T-lymphocytes with receptors for IgG were increased in HAE, but no difference in T-cell suppressor activity for B-cells was detected. Furthermore, increased IgG receptor expression was not accompanied by any significant changes in the ratios of OKT4- and OKT8-defined antigens. Numbers of peripheral mononuclear cells (MNC) detected by alpha-naphthyl acetate esterase (ANAE) staining positivity were not signif…

Immunohistochemical study of Langerhans cells in periapical lesions: correlation with inflammatory cell infiltration and epithelial cell proliferatio…

2008

Aim: The aim of this study is to determine the presence and distribution of Langerhans cells in periapical lesions, and correlate this with inflammatory cell infiltration and epithelial cell proliferation. Material and Methods: Seventy chronic dental periradicular lesions, obtained during periapical surgery from 70 patients, were included in this study, including: 46 granulomas, 18 scar tissue and 6 periradicular cysts. Immunohistochemical staining was performed using the following markers: CD3 to analyze the inflammatory infiltrate, CD1a to determine the presence of Langerhans cells and Ki67 to analyze the epithelial cell proliferation. The CD1a immunostaining density was established follo…

Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell–depleted reduced-intensity transplantation

2006

AbstractAllogeneic hematopoietic stem cell transplantation (SCT) regimens incorporating the lymphocytotoxic CD52 antibody alemtuzumab demonstrate efficient engraftment and reduced graft-versus-host disease (GVHD). However, these protocols substantially impair posttransplantation antiviral and antitumor immunity. To accelerate immune reconstitution after alemtuzumab-based reduced-intensity SCT, we administered prophylactic CD8-depleted donor lymphocyte infusions (DLIs) starting on days 60 and 120 after transplantation. DLIs were processed in an immunomagnetic good manufacturing practice depletion procedure resulting in a 2.5- to 6-log reduction in CD8 T cells. Of 23 high-risk patients with h…