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Biomedical subjects

Thomas Bieber

Publications and source records attributed to Thomas Bieber.

At least 19 recordsLinked to original sources
PubMed2003

Bullous lupus erythematosus in a patient with pre-existing dermatomyositis.

The group of autoimmune cutaneous connective tissue diseases (CCTD) includes systemic sclerosis, dermatomyositis (DM), lupus erythematosus (LE), and subtypes. Most CCTD patients can be assigned to one of these phenotypes or mixed forms, and transitions among the subsets exist. We present the case of a 26-year-old woman with bullous LE and a background of pre-existing DM. Observations of transitions between DM and LE are extremely rare. Nevertheless, this case demonstrates the close relationship between these two disorders in the context of autoimmune connective tissue disease.

Adult↗
PubMed2003

Atopic dermatitis.

Atopic dermatitis is a highly pruritic chronic inflammatory skin disorder affecting 10-20% of children worldwide. Symptoms can persist or begin in adulthood. It is also the most common cause of occupational skin disease in adults. This disease results from an interaction between susceptibility genes, the host's environment, pharmacological abnormalities, skin barrier defects, and immunological factors. New management approaches have evolved from advances in our understanding of the pathobiology of this common skin disorder.

Administration, Topical↗
PubMed2003

Allergic and nonallergic forms of atopic diseases.

Atopic dermatitis, allergic rhinitis, and asthma are atopic diseases that develop on a complex genetic background, the so-called atopic diathesis. Although they target different organs, in most patients they are characterized by the presence of elevated total serum IgE levels. However, a subgroup of atopic patients exhibits normal IgE levels and mechanisms contributing to the so-called "intrinsic" or "nonallergic form" have been the matter of intensive research work in the last years. Because of the rapid advancements in the research field of atopic diseases, it now becomes possible for the first time to delineate a new disease classification of allergic and nonallergic subtypes of atopic diseases, thereby bringing hope to the clinician for a more specific treatment approach for each subgroup of these patients.

Animals↗
PubMed2003

Characterization of dendritic cells from human oral mucosa: a new Langerhans' cell type with high constitutive FcepsilonRI expression.

BACKGROUND: The oral mucosa represents a unique immunologic unit with a high frequency of native allergen contact within the gastrointestinal tract in which immune tolerance is the natural outcome of allergen contact. Although Langerhans' cells (LC), known to play a crucial role in initiating allergen-dependent immune responses in the skin, have also been detected in the oral mucosa, little is known about their phenotype and exact physiologic role. OBJECTIVE: To elucidate whether LC from oral mucosa (oLC) differ from skin LC (sLC), these cells were subjected to detailed comparative analysis. METHODS: Crude epidermal and oral mucosa cell suspensions were prepared by trypsinization. oLC and sLC were compared phenotypically by flow cytometry techniques and functionally in T-cell proliferation assays. RESULTS: In contrast to sLC, freshly isolated oLC expressed significantly higher amounts of MHC class I and II, as well as costimulatory molecules CD40, CD80/B7.1, and CD86/B7.2. oLC displayed FcgammaRIII/CD16 and FcgammaRI/CD64. Most surprisingly, oLC constitutively expressed the high affinity receptor for IgE (FcepsilonRI) even in nonatopic donors. FcepsilonRI expression on oLC was further increased and correlated with the serum IgE levels in atopic individuals. oLC showed a higher allogeneic stimulatory activity than sLC, whereas the activation of autologous T cells correlated to the FcepsilonRI expression. CONCLUSION: Taken together, our results strongly indicate that oLC profoundly differ from their skin counterparts. The constitutive high expression of FcepsilonRI on oLC could point to particular skills of these cells within the regional immune system of the oral mucosa.

Antigens, CD↗
PubMed2003

Unraveling the mission of FcepsilonRI on antigen-presenting cells.

A decade ago, the discovery of the high-affinity receptor for IgE (FcepsilonRI) on epidermal Langerhans cells documented the end of the dogma that FcepsilonRI is only expressed on effector cells of anaphylaxis. Since then, the functional significance of this receptor on antigen-presenting cells (APCs) has been an area of intense research work. Scientists have focused on a better understanding of the molecular structure, regulation, and role of FcepsilonRI on APCs in the human immune system. Insights into the cellular events linked to the activation of APCs on ligation of FcepsilonRI by IgE and allergens might provide the basis for new aspects in the pathophysiology of allergic diseases and the design of future diagnostic and therapeutic strategies. This review is dedicated to the 10th anniversary of the discovery of FcepsilonRI on APCs and describes the numerous areas of research in this field.

Antigen-Presenting Cells↗
PubMed2003

Cellular immunotherapy after autologous hematopoietic stem cell transplantation: experimental strategies and clinical experiences.

Recurrence of disease after autologous hematopoietic stem cell transplantation is at least partly due to contamination of the reinfused transplant with tumor cells, thereby limiting the clinical outcome after transplantation. On the other hand, immunological effector cells are capable of purging bone marrow transplants in vitro and of destroying disseminated tumor cells in vivo. Cellular immunotherapy subsequent to autologous stem cell transplantation is therefore expected to have a major impact on recurrence rates of the disease. In this review, we present various strategies utilizing immunologic effector cells for elimination of disseminated tumor cells and discuss the advantages and limitations of cellular immunotherapy after autologous hematopoietic stem cell transplantation.

CD3 Complex↗
PubMed2003

Evidence for a differential expression of the FcepsilonRIgamma chain in dendritic cells of atopic and nonatopic donors.

While mast cells and basophils constitutively express the high-affinity IgE receptor (Fc epsilon RI), it is absent or weakly expressed on APCs from normal donors. Fc epsilon RI is strongly upregulated on APCs from atopic donors and involved in the pathophysiology of atopic diseases. Despite its clinical relevance, data about Fc epsilon RI regulation on APCs are scarce. We show that in all donors intracellular alpha chain of the Fc epsilon RI (Fc epsilon RI alpha) accumulates during DC differentiation from monocytes. However, expression of gamma chains of the Fc epsilon RI (Fc epsilon RI gamma), mandatory for surface expression, is downregulated. It is low or negative in DCs from normal donors lacking surface Fc epsilon RI (Fc epsilon RI(neg) DCs). In contrast, DCs from atopics express surface Fc epsilon RI (Fc epsilon RI(pos) DCs) and show significant Fc epsilon RI gamma expression, which can be coprecipitated with Fc epsilon RI alpha. In Fc epsilon RI(neg) DCs lacking Fc epsilon RI gamma, immature and core glycosylated Fc epsilon RI alpha accumulates in the endoplasmic reticulum. In Fc epsilon RI(pos) DCs expressing Fc epsilon RI gamma, an additional mature form of Fc epsilon RI alpha exhibiting complex glycosylation colocalizes with Fc epsilon RI gamma in the Golgi compartment. IgE binding sustains surface-expressed Fc epsilon RI on DCs from atopic donors dependent on baseline protein synthesis and transport and enhances their IgE-dependent APC function. We propose that enhanced Fc epsilon RI on DCs from atopic donors is driven by enhanced expression of otherwise limiting amounts of Fc epsilon RI gamma and is preserved by increased IgE levels.

Antigens↗
PubMed2002

Kinetics of gene induction after FcepsilonRI ligation of atopic monocytes identified by suppression subtractive hybridization.

The high-affinity receptor for IgE, FcepsilonRI, on APCs plays an important role in the initiation and chronicity of inflammatory atopic diseases. To understand the molecular regulation of FcepsilonRI-mediated processes, differentially expressed genes are of great interest to be identified. Suppression subtractive cDNA hybridization has been used to identify genes induced after FcepsilonRI stimulation on atopic monocytes. Overexpression of the identified genes was determined by semiquantitative RT-PCR analysis of transcripts from the tester (stimulated) and driver (unstimulated) monocytes. Results were confirmed and kinetics of the transcripts established using blood cells from additional atopics at 4 and 24 h of FcepsilonRI induction. The following sequences were identified: monocyte chemoattractant protein 1, macrophage-inflammatory protein 1beta, IL-6, beta(A) subunit of inhibin/activin, IFN-stimulated gene of 54 kDa, IL-1R antagonist, and kynurenine 3-monooxygenase. Chemokines are highly expressed during the early and late phase after FcepsilonRI cross-linking, whereas proinflammatory and differentiation stimuli rapidly decline after an initial overexpression. Kynurenine 3-monooxygenase, an enzyme involved in the degradation of the amino acid tryptophan, is significantly up-regulated during the late phase after 24 h of FcepsilonRI induction. These results demonstrate that the analysis of the profile of gene induction following activation of FcepsilonRI on atopic monocytes may reveal how these cells might participate in the regulation of atopic disorders.

Base Sequence↗
PubMed2002

FcepsilonRI induces the tryptophan degradation pathway involved in regulating T cell responses.

FcepsilonRI is suspected to play a pivotal role in the pathophysiology of atopic disorders such as atopic dermatitis. In search for genes differentially regulated by FcepsilonRI on APCs, a differential cDNA bank of receptor-stimulated and unstimulated monocytes was established. By means of suppression subtractive hybridization, we identified kynurenine 3-monooxygenase and subsequently indoleamine 2,3-dioxygenase (IDO) to be overexpressed in FcepsilonRI-activated monocytes. IDO is the rate-limiting enzyme in the catabolism of the essential amino acid tryptophan. We show that cross-linking of FcepsilonRI on monocytes results in low tryptophan concentrations associated with impaired T cell stimulatory capacity. Importantly, T cell suppression could be prevented by the addition of tryptophan or inhibition of IDO. Moreover, stimulation of T cells by FcepsilonRI-activated monocytes was increased compared with T cell stimulation by nonactivated monocytes if exogenous supply of tryptophan was available. We speculate that the expression of IDO by FcepsilonRI(+) APCs in vivo allows these cells to regulate T cell responses in atopic disorders by inhibiting or stimulating T cell proliferation, depending on the metabolic environment.

Antigen-Presenting Cells↗
PubMed2002

A reducing microenvironment leads to the generation of FcepsilonRIhigh inflammatory dendritic epidermal cells (IDEC).

Inflammatory dendritic epidermal cells present in skin lesions of the atopic eczema/dermatitis syndrome display the highest expression of the high-affinity receptor for IgE (FcepsilonRI), ever detected on human antigen-presenting cells. Owing to the instability of the FcepsilonRI (alphagammagamma) complex and fast cleavage from the cell surface during the interleukin-4/granulocyte-macrophage colony-stimulating factor driven in vitro differentiation of monocytes, a method to generate inflammatory dendritic epidermal cells was not at our disposal in the past and the amount of ex vivo isolated inflammatory dendritic epidermal cells available for functional assays was limited. Therefore, information about the role of inflammatory dendritic epidermal cells and FcepsilonRI on this dendritic cell subtype in atopic and inflammatory skin diseases is completely missing. In this study, we were able to: (i) increase the expression of a functional FcepsilonRI complex on the cell surface of immature monocyte-derived dendritic cells from atopic donors by creating a reducing microenvironment; (ii) enhance significantly the intracellular pool of the FcepsilonRIgamma chains, which is the limiting parameter for the FcepsilonRI surface expression; and (iii) generate monocyte-derived dendritic cells displaying the phenotypical characteristics of inflammatory dendritic epidermal cells, producing high amounts of proinflammatory cytokines and chemokines similar to the cytokines found in lesional skin of the atopic eczema/dermatitis syndrome. Altogether the high expression of functional FcepsilonRI on these cells enables us for the first time to study inflammatory dendritic epidermal cells and FcepsilonRI-mediated mechanisms of inflammatory dendritic epidermal cells in vitro, in order to shed light on the putative role of this important cell type in the atopic eczema/dermatitis syndrome.

Cells, Cultured↗
PubMed2002

Dichotomic nature of atopic dermatitis reflected by combined analysis of monocyte immunophenotyping and single nucleotide polymorphisms of the interleukin-4/interleukin-13 receptor gene: the dichotomy of extrinsic and intrinsic atopic dermatitis.

Patients with atopic dermatitis display substantial immunologic abnormalities, among which elevated total IgE is considered as a hallmark; however, a subgroup of atopic dermatitis patients exhibits normal IgE levels, but mechanisms contributing to the so-called "intrinsic" or "nonallergic" form of atopic dermatitis are obscure. In order to unravel similarities and differences of both atopic dermatitis subtypes, the phenotype of monocytes, total serum IgE levels, and serum levels of cytokines regulating the IgE production from nonatopic individuals and patients with allergic rhinitis, and extrinsic and intrinsic atopic dermatitis were measured. Concomitantly, genomic DNA probes of all subjects were analyzed for single nucleotide polymorphisms of candidate genes of structures involved in the regulation of the IgE synthesis, such as interleukin-4 and the interleukin-4R/interleukin-13R. Our data show that the surface expression of the high- and low-affinity receptor for IgE (FcepsilonRI and FcepsilonRII/CD23) and the interleukin-4Ralpha chain were significantly elevated in monocytes from patients with extrinsic atopic dermatitis. Furthermore, serum levels of interleukin-13 were significantly increased in patients with intrinsic atopic dermatitis. In addition, the frequency of the interleukin-4Ralpha polymorphism C3223T and the interleukin-4 polymorphism C590T tended to be higher in extrinsic atopic dermatitis than in intrinsic atopic dermatitis. Altogether our findings indicate that intrinsic atopic dermatitis patients exhibit phenotypic and immunologic features, which differ from those of patients with extrinsic atopic dermatitis or other atopic disorders.

Adolescent↗
PubMed2002

Enhanced expression and activity of protein-tyrosine kinases establishes a functional signaling pathway only in FcepsilonRIhigh Langerhans cells from atopic individuals.

The trimeric high-affinity IgE receptor (FcepsilonRI) on human epidermal Langerhans cells mediates IgE-dependent antigen uptake and subsequent antigen focusing. Its expression is upregulated on Langerhans cells (FcepsilonRIhigh Langerhans cells) and inflammatory dendritic epidermal cells (FcepsilonRIhigh inflammatory dendritic epidermal cells) in the skin of patients with atopic dermatitis. In the absence of the amplifying beta-chain in these cells, FcepsilonRI signaling (indicated by calcium mobilization and activation of the transcription factor nuclear factor-kappaB) is only detectable in FcepsilonRIhigh Langerhans cells from atopics, but not FcepsilonRIlow Langerhans cells from nonatopics. Therefore we investigated protein-tyrosine kinases putatively involved in FcepsilonRI signaling in Langerhans cells and asked whether differences in their expression and FcepsilonRI-induced activity could explain the dichotomic responses observed in atopic vs nonatopic individuals. First, we found the src protein-tyrosine kinases p53/56lyn, p59fyn, p56/59hck, p55c-fgr, and p60c-src to be expressed in Langerhans cells from all donors. In addition, whereas p56lck was lacking, p72syk and the negative regulatory p50csk were detected. Upon terminal maturation of Langerhans cells in vitro, no significant change of the protein- tyrosine kinase expression profile except downregulation of p56/59hck was observed. In contrast, significant upregulation of all protein-tyrosine kinase expressed except p50csk was detected in FcepsilonRIhigh Langerhans cells, but not in FcepsilonRIhigh inflammatory dendritic epidermal cells. Finally, the important protein-tyrosine kinases substrate phospholipase C-gamma1, which is also essential for downstream calcium mobilization, was only phosphorylated upon FcepsilonRI triggering in FcepsilonRIhigh Langerhans cells from atopics, but not in FcepsilonRIlow Langerhans cells from nonatopics. Therefore, upregulation of FcepsilonRI and protein-tyrosine kinase expression as well as subsequent protein-tyrosine kinase activity may explain, at least in part, that an efficient signaling pathway in terms of calcium mobilization is restricted to FcepsilonRIhigh Langerhans cells from atopic individuals. Key words:

Cell Line↗