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Biomedical subjects

Thomas Bieber

Publications and source records attributed to Thomas Bieber.

At least 55 records · Page 3Linked to original sources
PubMed2004

Normalized proliferation of normal and psoriatic keratinocytes by suppression of sAPPalpha-release.

The soluble form of the beta-amyloid precursor protein (sAPPalpha) is known to function in the autocrine regulation of epidermal growth and repair. Here we show that its proteolytic release by alpha-secretase in normal human keratinocytes is susceptible to hydroxamic-acid-based zinc metalloproteinase inhibitors and suppressed by these inhibitors by 80%-90%. As various other growth factors participate in regulating epidermal growth we investigated whether the inhibitor-induced sAPPalpha-deficiency would affect keratinocyte proliferation. At optimal inhibitor concentrations the suppression of sAPPalpha-release was followed by a decline in proliferation by 50%-60%, indicating that sAPPalpha is a major growth factor that cannot be compensated for by other growth factors. This finding was the basis for the treatment of human lesional psoriatic keratinocytes with these inhibitors, which resulted in the normalization of their increased proliferation rates. The reversibility of these effects and the lack of toxicity underline the value of these inhibitors and suggest their therapeutic application in psoriatic skin diseases.

Adult↗
PubMed2004

Transforming growth factor-beta1 regulates the expression of the high-affinity receptor for IgE on CD34 stem cell-derived CD1a dendritic cells in vitro.

It has been reported that monocytes, Langerhans cells (LC) and other dendritic cells (DC) express the high-affinity receptor for IgE (FcepsilonRI) in patients with atopic diseases. These cells may be instrumental in the control of the immune response and the allergic inflammation. In this context, transforming growth factor beta 1 (TGF-beta1) has been highlighted as a key cytokine involved in the mechanisms aimed to orchestrate tolerance and has been suggested as a candidate gene in atopic diseases. In this report, we investigate the putative role of TGF-beta1 in the regulation of FcepsilonRI on cord blood CD34+ stem cell-derived CD1a+ DC (CD34-derived CD1a+ DC). Kinetic experiments show that FcepsilonRI spontaneously appears on the surface of CD1a+ DC, but decreases when exogenous TGF-beta1 is added at high doses (10 ng per mL) or when endogenous TGF-beta1 is neutralized in the culture conditions. In contrast, low-dose TGF-beta1 (0.5 ng per mL) stabilizes surface FcepsilonRI expression on DC. Increasing TGF-beta1 concentrations leads to the generation of LC-like DC showing an augmentation in stimulatory capacity towards allogeneic T cells. In view of these data, a picture emerges that FcepsilonRI+ on DC is finely modified by the TGF-beta1 concentration in the microenvironment and could be of primary relevance in the context of atopic diseases.

Antigens, CD1↗
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

The good, the bad and the ugly--APCs of the eye.

Dendritic-cell (DC) populations throughout the body have a wide range of features in common, which are associated with their primary function in antigen presentation. The unique immune milieu of the anterior segment of the eye is characterized by a selective DC-dependent inability to develop delayed hypersensitivity responses following antigen invasion into the eye. Recent research papers provide evidence that different maturation stages of DC subsets are detectable at different corneal sites. Thus, the corneal DC, as well as the DC and the macrophages in the iris and ciliary body, have the potential of determining the outcome of immunity or tolerance within this organ.

Animals↗
PubMed2003

Immune mechanisms leading to atopic dermatitis.

The incidence of atopic dermatitis is increasing, and this poses a major burden on health care costs. A precise understanding of the genetic and immunologic mechanisms is crucial for development of effective treatment strategies for atopic dermatitis. Various studies indicate that it has a multifactorial cause, with activation of complex immunologic and inflammatory pathways. The current review will examine recent advances that have been made in our understanding of the genetic and pathophysiologic prerequisites that form the basis of this common recalcitrant skin disorder.

Dermatitis, Atopic↗
PubMed2003

Indoleamine 2,3-dioxygenase-expressing antigen-presenting cells and peripheral T-cell tolerance: another piece to the atopic puzzle?

There is growing evidence that dendritic cells, the major antigen-presenting cells and T-cell activators, have a broad effect on peripheral T-cell tolerance and regulation of immunity. Very recently, a new feature of regulatory antigen-presenting cells was observed. Certain dendritic cells, monocytes, and macrophages express the enzyme indoleamine 2,3-dioxygenase, and thus because of enhanced degradation of the essential amino acid tryptophan, they modulate T-cell activity in specific local tissue environments. In this review we discuss the various and apparently disparate effects of indoleamine 2,3-dioxygenase induction in cells of the immune system. We place current knowledge about this mechanism in the context of atopy. We introduce the hypothesis that tryptophan degradation might add to the ability to control and downregulate allergen-specific T-cell responses in atopic individuals.

Antigen-Presenting Cells↗
PubMed2003

[Systemic treatment of cutaneous lupus erythematosus].

The treatment of cutaneous lupus erythematosus (CLE) remains a therapeutic challenge. In many cases, systemic treatment of the disease is necessary, especially in cases resistant to topical treatment or with internal organ involvement. Even though many different agents can be employed in this situation, most are not approved in Germany for the treatment of CLE. We give an overview of the agents used in the systemic treatment of CLE and review their mechanisms of action, indications and their practical use in cutaneous LE based on literature results and our own experience. We discuss corticosteroids, antimalarials, dapsone, azathioprine, cyclophosphamide, methotrexate, retinoids, cyclosporine A, mycophenolate mofetil, sulfasalazine, thalidomide, clofazimine, tacrolimus, immunoglobulins, monoclonal antibodies, plasmapheresis, etanercept, infliximab, feflunomid, gold and interferon-alpha.

Acute Disease↗
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

Dendritic cells and atopic eczema/dermatitis syndrome.

PURPOSE OF REVIEW: The manifestation of atopic eczema/dermatitis syndrome is believed to result from a complex interrelationship of environmental factors, pharmacological abnormalities, skin barrier defects, and immunological phenomena. Although we are only beginning to understand the molecular basis of this disease, much progress has been made in defining key events leading to the manifestation of allergic inflammation. Here, we review recent findings that underscore the importance of dendritic cells as being central to shape these proinflammatory responses. RECENT FINDINGS: Evidence for a differential regulation of the high affinity receptor for IgE, Fc epsilon RI, on the surface of atopic dendritic cells compared with non-atopic dendritic cells became apparent. In atopic donors, in contrast to non-atopic donors, the intracellular expression of the gamma-chains of Fc epsilon RI is sufficient, thus leading to the assembly with the alpha-chain and surface expression of the receptor. This finding is of considerable interest for an understanding of the pathophysiology of IgE-mediated dendritic cell functions in atopic eczema/dermatitis syndrome. In addition, it has been shown that keratinocytes from the epidermal skin of individuals with atopic eczema/dermatitis syndrome express human thymic stromal lymphopoietin, which activates dendritic cells to attract T helper type 2 cells into the skin. Furthermore, these activated dendritic cells prime naïve T cells into T helper type 2 cells. SUMMARY: The past few years have seen a remarkable process of refocusing in atopy. Dendritic cells in particular have been at the centre of this process. It has become unequivocally clear that these cells have the power of shaping the allergic response.

Dendritic Cells↗