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Bernhard Moser

Publications and source records attributed to Bernhard Moser.

At least 19 recordsLinked to original sources
PubMed2006

Murine CXCL14 is dispensable for dendritic cell function and localization within peripheral tissues.

Dendritic cells (DCs) have long been recognized as key regulators of immune responses. However, the process of their recruitment to peripheral tissues and turnover during homeostasis remains largely unknown. The chemokine CXCL14 (BRAK) is constitutively expressed in skin and other epithelial tissues. Recently, the human chemokine was proposed to play a role in the homeostatic recruitment of macrophage and/or DC precursors toward the periphery, such as skin. Although so far no physiological function could be demonstrated for the murine CXCL14, it shows a remarkable homology to the human chemokine. In order to elucidate the in vivo role of CXCL14, we generated a mouse defective for this chemokine. We studied various components of the immune system with emphasis on monocytes/macrophages and DC/Langerhans cell (LC) populations in different tissues during steady state but did not find a significant difference between knockout (CXCL14(-)(/)(-)) and control mice. Functionally, LCs were able to become activated, to migrate out of skin, and to elicit a delayed type of hypersensitivity reaction. Overall, our data indicate that murine CXCL14 is dispensable for the homeostatic recruitment of antigen-presenting cells toward the periphery and for LC functionality.

Animals↗
PubMed2006

Infection with a periodontal pathogen increases mononuclear cell adhesion to human aortic endothelial cells.

BACKGROUND: As a link between periodontal infections and an increased risk for vascular disease has been demonstrated, we assessed the ability of the Gram-negative periodontal pathogen Porphyromonas gingivalis to modulate properties of endothelial cells linked to inflammation and proatherogenic pathways. METHODS AND RESULTS: Primary human aortic endothelial cells (HAEC) were infected with either P. gingivalis strain 381 or its non-invasive fimbriae-deficient mutant, DPG3, and incubated with U-937 monocytes, or Jurkat T cells. P. gingivalis-infected HAEC demonstrated significantly increased adhesion of immune cells compared to non-infected cells or those infected with DPG3. Heat-killed bacteria had no effect on mononuclear cell adhesion and P. gingivalis LPS had only a minimal effect. P. gingivalis infection significantly increased HAEC expression of VCAM-1, ICAM-1 and E-selectin, and enhanced production of IL-6, IL-8 and MCP-1. CONCLUSION: These data demonstrate that live invasive P. gingivalis 381 elicits a pro-atherogenic response in HAEC.

Aorta↗
PubMed2006

Homing and function of human skin gammadelta T cells and NK cells: relevance for tumor surveillance.

Normal (noninflamed) human skin contains a network of lymphocytes, but little is known about the homing and function of these cells. The majority of alphabeta T cells in normal skin express CCR8 and produce proinflammatory cytokines. In this study we examined other subsets of cutaneous lymphocytes, focusing on those with potential function in purging healthy tissue of transformed and stressed cells. Human dermal cell suspensions contained significant populations of Vdelta1(+) gammadelta T cells and CD56(+)CD16(-) NK cells, but lacked the subsets of Vdelta2(+) gammadelta T cells and CD56(+)CD16(+) NK cells, which predominate in peripheral blood. The skin-homing receptors CCR8 and CLA were expressed by a large fraction of both cell types, whereas chemokine receptors associated with lymphocyte migration to inflamed skin were absent. Neither cell type expressed CCR7, although gammadelta T cells up-regulated this lymph node-homing receptor upon TCR triggering. Stimulation of cutaneous Vdelta1(+) gammadelta T cell lines induced secretion of large amounts of TNF-alpha, IFN-gamma, and the CCR8 ligand CCL1. In contrast to cutaneous alphabeta T cells, both cell types had the capacity to produce intracellular perforin and displayed strong cytotoxic activity against melanoma cells. We therefore propose that gammadelta T cells and NK cells are regular constituents of normal human skin with potential function in the clearance of tumor and otherwise stressed tissue cells.

Cell Movement↗
PubMed2006

Gammadelta T cells: an alternative type of professional APC.

A subtype of activated human gammadelta T cells, termed Vdelta2+ T cells, has antigen-presentation features similar in potency and efficacy to those seen in dendritic cells. Comparable treatment of alphabeta T cells does not result in 'professional' antigen presenting cells (APCs). What is so special about Vdelta2+ T cells? How do they acquire these unexpected properties? Under what physiological conditions would such a bridge between innate and adaptive immunity come into play? In addition to discussing these questions, we introduce a model that correlates the expression of lymph node homing receptors in Vdelta2+ T cells with the involvement of this alternative type of APC in anti-microbial alphabeta T cell responses.

Antigen Presentation↗
PubMed2006

Invited commentary.

Explore the source record for details and available documents.

Disease Susceptibility↗
PubMed2006

Apoptosis-specific activation markers in on- versus off-pump coronary artery bypass graft (CABG) patients.

BACKGROUND: The relation of epithelial/endothelial apoptosis and secretion of death-inducing receptors (DIR) in comparison to vascular adhesion molecules is not known in patients undergoing the On- versus Off-pump coronary artery bypass graft (CABG) procedure. METHODS: 30 patients were prospectively included in the study (On- vs. Off-pump CABG, each n = 15). Serum samples were obtained prior to, and 30 minutes, 60 minutes and 24 hours after CABG operation. ELISA was utilized to detect caspase-cleaved cytokeratin-18 (CK18) by means of M30 antibody, soluble VCAM-1, soluble ICAM-1, and soluble DIR TNFR-1 and CD95. RESULTS: Soluble caspase-cleaved CK18 was increased and leveled to initial values at 24 hrs. sICAM-1 showed a significant decrease at 30 minutes and 60 minutes in comparison to preoperative values. sTNFR-1/sCD95 showed a rise that was not significant to preoperative values. CONCLUSION: These results indicate for the first time that epithelial/endothelial apoptosis is occurring in patients undergoing bypass operation, irrespective of the CABG procedure selected.

Apoptosis↗
PubMed2005

Soluble RAGE: a hot new biomarker for the hot joint?

The receptor for advanced glycation endproducts (RAGE) interacts with distinct ligand families linked to the inflammatory response. Studies in animal models suggest that RAGE is upregulated in the inflamed joint and that blockade of the receptor, using a ligand decoy soluble form of RAGE (sRAGE), attenuates joint inflammation and expression of inflammatory and tissue-destructive mediators. In this issue of Arthritis Research & Therapy, Rille Pullerits and colleagues reported that plasma levels of sRAGE were reduced in subjects with rheumatoid arthritis compared with healthy controls or subjects with non-inflammatory joint disease. These findings suggest the possibility that levels of sRAGE might be a biomarker of inflammation. Not resolved by these studies, however, is the intriguing possibility that endogenously higher levels of sRAGE might be linked to a lower incidence of arthritis or to the extent of inflammation. Nevertheless, although 'cause or effect' relationships may not be established in this report, fascinating insights into RAGE, inflammation and human arthritis emerge from these studies.

Animals↗
PubMed2005

Professional antigen-presentation function by human gammadelta T Cells.

Human gammadelta T cells are considered to play a vital role in protective immunity through cytokine secretion and cytotoxic activity. We report that cells expressing the Vgamma2Vdelta2+-T cell receptor (Vdelta2+ T cells) also display principal characteristics of professional antigen-presenting cells such as dendritic cells. Thus, when activated, these cells efficiently processed and displayed antigens and provided co-stimulatory signals sufficient for strong induction of naïve alphabeta T cell proliferation and differentiation. We suggest that, upon microbial activation, Vdelta2+ T cells participate in the induction of adaptive immune responses and that these cells may be a useful tool in vaccine development and immunotherapy.

Antigen Presentation↗
PubMed2005

Cutaneous CXCL14 targets blood precursors to epidermal niches for Langerhans cell differentiation.

Dendritic cells (DCs) are major constituents of peripheral tissues, where they control immunity to foreign and self-antigens. The process of continuous DC renewal under homeostatic conditions is largely undefined. Here, we demonstrate that CD14+ DC precursors, either derived from CD34+ hematopoietic progenitor cells or isolated from blood, were attracted by the chemokine CXCL14, which is constitutively produced in healthy skin and other epithelial tissues. In a tissue model we show that human epidermal equivalents profoundly affected CD14+ DC precursors, including their suprabasal positioning and survival as well as their differentiation into Langerhans cell-like cells with potent antigen-presentation functions. Our model assigns unprecedented roles to CXCL14 and epidermal tissue as attractant and niche of differentiation, respectively, in the renewal of Langerhans cells under steady-state conditions.

Cell Differentiation↗
PubMed2005

Follicular B helper T cells in antibody responses and autoimmunity.

T-cell help for B cells is essential for high-affinity antibody responses and B-cell memory. Recently, the identity of a discrete follicular population of T cells that has a crucial role in this process has become clearer. Similar to primed CD4(+) T cells in the tonsils and memory CD4(+) T cells in the peripheral blood, this follicular population of T cells expresses CXC-chemokine receptor 5 (CXCR5). Owing to their distinct homing preferences and helper function, these T cells differ from T helper 1 and T helper 2 cells and have been denoted follicular B helper T cells. Here, we outline the central role of this subset in normal and pathological immune responses.

Animals↗
PubMed2005

Receptor for advanced glycation end products and its ligands: a journey from the complications of diabetes to its pathogenesis.

Many studies have suggested that the expression of RAGE (receptor for advanced glycation end products) is upregulated in human tissues susceptible to the long-term complications of diabetes. From the kidneys to the macrovessels of the aorta, RAGE expression is upregulated in a diverse array of cell types, from glomerular epithelial cells (podocytes) to endothelial cells, vascular smooth muscle cells, and inflammatory mononuclear phagocytes and lymphocytes. Although RAGE was first described as a receptor for advanced glycation end products (AGEs), the key finding that RAGE was also a signaling receptor for proinflammatory S100/calgranulins and amphoterin, led to the premise that even in euglycemia, ligand-RAGE interaction propagated inflammatory mechanisms linked to chronic cellular perturbation and tissue injury. Indeed, such considerations suggested that RAGE might even participate in the pathogenesis of type 1 diabetes. Our studies have shown that pharmacological and/or genetic deletion/mutation of the receptor attenuates the development of hyperglycemia in NOD mice; in mice with myriad complications of diabetes, interruption of ligand-RAGE interaction prevents or delays the chronic complications of the disease in both macro- and microvessel structures. Taken together, these findings suggest that RAGE is "at the right place and time" to contribute to the pathogenesis of diabetes and it complications. Studies are in progress to test the premise that antagonism of this interaction is a logical strategy for the prevention and treatment of diabetes.

Animals↗
PubMed2005

Chemokines: control of primary and memory T-cell traffic.

Motility is a hallmark of leukocytes, and breakdown in the control of migration contributes to many inflammatory diseases. Chemotactic migration of leukocytes largely depends on adhesive interaction with the substratum and recognition of a chemoattractant gradient. Chemokines are secreted proteins and have emerged as key controllers of integrin function and cell locomotion. Numerous distinct chemokines exist that target all types of leukocytes, including hematopoietic precursors, leukocytes of the innate immune system, as well as naive memory, and effector lymphocytes. The combinatorial diversity in responsiveness to chemokines ensures the proper tissue distribution of distinct leukocyte subsets under normal and pathological conditions. Inflammatory chemokines are readily detected in lesional tissue and local cellular infiltrates carry corresponding chemokine receptors. Blocking of inflammatory chemokines represents a promising strategy for the development of novel anti-inflammatory therapeutics. This review focuses on a separate class of chemokines, termed homeostatic chemokines, with steady-state production at diverse sites, including primary and secondary lymphoid tissues as well as peripheral (extralymphoid) tissues. More precisely, we discuss the chemokines involved in T-cell traffic during the initiation of adaptive immunity and compare the distinct migration properties of short-lived effector T cells and long-lived memory T cells. Memory T cells are currently classified according to the presence of the lymph node-homing receptor CCR7 into CCR7+ central memory T (T(CM)) cells and CCR7- effector memory T (T(EM)) cells. For better understanding memory T-cell function, we propose the distinction of a third category, termed peripheral immune surveillance T (T(PS)) cells, which typically reside in healthy peripheral tissues, such as skin, lung, and gastrointestinal tract. Localization and relocation of memory T cells is strictly related to their function in recall responses. Therefore, detailed knowledge of their generation and tissue distribution may help to design better vaccination strategies.

Animals↗
PubMed2005

Soluble ST2 protein in cardiac surgery: a possible negative feedback loop to prevent uncontrolled inflammatory reactions.

BACKGROUND: Recent reports have demonstrated that cardiopulmonary bypass (CBP) utilization leads to a TH2 cytokine bias in patients undergoing coronary artery bypass grafting (CABG) operation. The relation of soluble ST2 and secretion of IL-10, markers of TH2 T-cell activation, and IL-13 in relation to immunoglobulin isotope production is not known in patients undergoing On- versus Off-pump (CABG) procedure. METHODS: 30 patients were prospectively included in the study (On- vs Off-pump CABG, each n = 15). Serum samples were obtained prior to, and 30 min, 60 min and 24hrs after operation. ELISA was utilized to detect sST2 and IL-10, IL-13 and immunoglobulin isotype production. RESULTS: In both cohorts we could demonstrate a significant rise of ST2 24 hours after the CABG procedure. In the On-pump group ST2 levels (pg/ml) before the operation, at 30 and 60 minutes and after 24 hours were 115.3 +/- 25, 71.2 +/- 15, 114.1 +/- 26 and 4231.9 +/- 520, respectively. In the Off-pump group they were 200.3 +/- 109, 91.2 +/- 20, 137 +/- 29 and 4144.9 +/- 488 (both, p < 0.0001, p < 0.0001, respectively). IL-10 (pg/ml) levels rose from preoperative values of 6.2 +/- 1.6 in the On-pump group and 7.91 +/- 1.8 in the Off-pump group to 33.14 +/- 8.7 and 13.72 +/- 3 after 60 minutes (p 0.0189, p 0.0397, respectively). IL-13 levels and immunoglobulin production did not change significantly within the study period irrespective of the operation procedure used. CONCLUSION: In conclusion, our results demonstrate that sST2 and IL-10, markers of TH2 cytokine producing cells, are increased in CABG operation, irrespective of the procedure selected, and settles a longstanding controversy concerning the shift from Th1 to Th2 cells.

Cardiopulmonary Bypass↗
PubMed2004

Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues.

Antigen-driven T cell education and subsequent pathogen elimination present particular challenges for the immune system. Pathogens generally enter the body at peripheral sites such as the skin, gastrointestinal tract or lung, areas from which naïve T cells are largely excluded. Instead, naïve T cells constantly recirculate through secondary lymphoid organs, such as lymph nodes and Peyer's patches, in search for antigen brought to these locations by means of afferent lymphatic channels. Here, antigen-loaded dendritic cells present antigen-peptide-MHC complexes to clonotypic T cells and provide appropriate co-stimulatory signals for immune response initiation. As a result, short-lived effector T cells and long-lived memory T cells are generated that reach the peripheral tissue for participation in immune responses and immune surveillance. Effector and memory T cell relocation is non-random, due to tissue-specific "address codes" that allow proper tissue homing. This process involves adhesion molecules, including selectins, integrins, and corresponding vascular ligands as well as the large family of chemokines and their receptors. Here, we discuss the changes in chemokine receptor expression that occur during T cell activation and differentiation, and the ways in which these changes impact on the migration potential of naïve, effector, and memory T cells. We summarize our current understanding of T cell homing to the T zone and B cell follicles within secondary lymphoid tissues and highlight the two chemokine receptors CCR7 and CXCR5 that recognize chemokines constitutively present either in the T zone (CCR7 ligands CCL19/ELC and CCL21/SLC) or follicular compartment (CXCR5 ligand CXCL13/BCA-1). CCR7 is characteristic for naive and central memory T (T(CM)) cells whereas CXCR5 distinguishes follicular B helper T (T(FH)) cells. In addition, we further subdivide long-lived memory T cells into CCR7-negative effector memory T (T(EM)) cells and peripheral immune surveillance T (T(PS)) cells. The latter term designates the extraordinarily large subset of memory T cells with primary residence in normal (healthy) peripheral tissues. Our current understanding of T(PS) cell migration and function is highly fragmentary, but these cells are thought to provide immediate protection locally at the site of pathogen entry. Here, we propose that the tissue distribution of T(PS) cells is determined by a distinct set of chemokines and corresponding receptors that differs from those operating in secondary lymphoid tissues and inflammatory sites.

Animals↗