Consumer-Based Ranking for Strategic Selection of IoT Business Models

The digitization of business environments requires companies to be more consumer-centric than before. In the course of these adjustments, managers operate in the area of conflict between value creation for the firm, consumers’ limited willingness to pay for products and services, and the need to gain and maintain consumers’ trust. To support managers in the challenge to redefine their business models to fit the new digitized business environment, we suggest that managers should incorporate consumer\u27s attitudes towards Internet of Things (IoT) business models in their strategic business model choice. Based on a choice experiment with 301 individuals, we identified a set of business models ranked according to the probability that users are most likely to agree with, and thus accept. The results of the study provide direct indications about which IoT business models are from a consumer perspective desirable and which not so that managers can directly implement these insights in practice

The ENTOURAGE Privacy and Security Reference Architecture for Internet of Things Ecosystems

The Internet of Things (IoT), with its ubiquitous sensors and actuators, enables highly useful novel use cases, notably in the field of digital assistance. It also raises unprecedented privacy and security issues. This contribution presents a reference architecture for an ecosystem of digital assistants with minimal barriers of entry, that aims to be both secure and privacy-respecting. We present concise definitions, requirements, and a layered architectural structure for IoT assistants. Moreover, we introduce privacy and security assistants building on privacy patterns such as privacy dashboard, privacy mode and security and privacy policies and interface

CD4-mediated functional activation of human CD4 CD25 regulatory T cells

Naturally occurring CD4( )CD25( )FoxP3( ) regulatory T cells (CD25( ) Tregs) constitute a specialized population of T cells that is essential for the maintenance of peripheral self-tolerance. The immune regulatory function of CD25( ) Tregs depends upon their activation. We found that anti-CD4 antibodies activate the suppressive function of human CD25( ) Tregs in a dose-dependent manner. We demonstrate that CD4-activated CD25( ) Tregs suppress the proliferation of CD4( ) and CD8( ) T cells, their IL-2 and IFN-gamma production as well as the capacity of CD8( ) T cells to re-express CD25. By contrast, anti-CD4 stimulation did not induce suppressive activity in conventional CD4( ) T cells. These results identify CD4 as a trigger for the suppressive function of CD25( ) Tregs and suggest a possible CD4-mediated exploitation of these cells

Dendritic cells : sentinels of immunity and tolerance

The induction of effective antigen-specific T-cell immunity to pathogens without the initiation of autoimmunity has evolved as a sophisticated and highly balanced immunoregulatory mechanism. This mechanism assures the generation of antigen-specific effector cells as well as the induction and maintenance of antigen-specific tolerance to self-structures of the body. As professional antigen-presenting cells of the immune system, dendritic cells (DC) are ideally positioned throughout the entire body and equipped with a unique capability to transport antigens from the periphery to lymphoid tissues. There is growing evidence that DC, besides their well-known immunostimulatory properties, also induce and regulate T-cell tolerance in the periphery. This regulatory function of DC is strictly dependent on their different stages of maturation and activation. Additionally, immunosuppressive agents and cytokines further influence the functions of maturing DC. The regulatory properties of DC include induction of T-cell anergy, apoptosis, and the generation of T-cells with regulatory capacities. This brief review summarizes the current knowledge about the immunoregulatory role of DC as guardians for the induction of T-cell immunity and tolerance

Human CD25+ regulatory T cells : two subsets defined by the integrins α4β7 or α4β1 confer distinct suppressive properties upon CD4+ T helper cells

Down‐regulation of autoreactive T cell responses in vivo includes cell‐contact‐dependent as well as contact‐independent mechanisms. Infectious tolerance is a contact‐dependent mechanism used by naturally occurring CD25+ T regulatory cells (Tregs) to confer suppressive activity upon conventional CD4+ T cells thereby generating secondary T helper suppressor cells(Thsup), which inhibit T cell activation via soluble mediators. Here, we describe two distinct subsets of human Tregs, characterized by expression of either the α4β7 integrin or the α4β1 integrin. Upon activation, both subsets show an enhanced expression of FoxP3, recently described as a key transcription factor of murine Tregs. In addition, both are able to convey suppressive capacity to conventional CD4+ T cells. However, the properties of Treg subsets are rather distinct: α4β7+Tregs induce IL‐10‐producing Thsup (Tr1‐like), whereas α4β1+ Tregs induce TGF‐β‐producing Thsup (Th3‐like). Our findings reconcile conflicting results by clearly demonstrating that suppression through naturally occurring CD25+ Tregs is primary cell‐contact‐dependent but is subsequently followed by cell‐contact‐independent T cell inhibition mediated by second‐generation Tr1‐ and Th3‐like Thsup via the soluble factors IL‐10 and TGF‐β

Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells

Naturally occurring CD4( )CD25( ) regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses. Therefore, approaches to modulate Treg function in vivo could provide ways to enhance or reduce immune responses and lead to novel therapies. Here we show that the CD4 binding human immunodeficiency virus-1 envelope glycoprotein gp120 is a useful and potent tool for functional activation of human Tregs in vitro and in vivo. Gp120 activates human Tregs by binding and signaling through CD4. Upon stimulation with gp120, human Tregs accumulate cyclic adenosine monophosphate (cAMP) in their cytosol. Inhibition of endogeneous cAMP synthesis prevents gp120-mediated Treg activation. Employing a xenogeneic graft versus host disease model that has been shown to be applicable for the functional analysis of human Tregs in vivo, we further show that a single dose of gp120 is sufficient to prevent lethal graft versus host disease and that the tolerizing effect of gp120 is strictly dependent on the presence of human Tregs and their up-regulation of cAMP upon gp120-mediated activation. Our findings demonstrate that stimulation via the CD4 receptor represents a T-cell receptor-independent Treg activating pathway with potential to induce immunologic tolerance in vivo

miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression.

BackgroundIn humans and mice naturally occurring CD4(+)CD25(+) regulatory T cells (nTregs) are a thymus-derived subset of T cells, crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Recent work using Dicer-deficient mice irrevocably demonstrated the importance of miRNAs for nTreg cell-mediated tolerance.Principal findingsDNA-Microarray analyses of human as well as murine conventional CD4(+) Th cells and nTregs revealed a strong up-regulation of mature miR-155 (microRNA-155) upon activation in both populations. Studying miR-155 expression in FoxP3-deficient scurfy mice and performing FoxP3 ChIP-Seq experiments using activated human T lymphocytes, we show that the expression and maturation of miR-155 seem to be not necessarily regulated by FoxP3. In order to address the functional relevance of elevated miR-155 levels, we transfected miR-155 inhibitors or mature miR-155 RNAs into freshly-isolated human and mouse primary CD4(+) Th cells and nTregs and investigated the resulting phenotype in nTreg suppression assays. Whereas miR-155 inhibition in conventional CD4(+) Th cells strengthened nTreg cell-mediated suppression, overexpression of mature miR-155 rendered these cells unresponsive to nTreg cell-mediated suppression.ConclusionInvestigation of FoxP3 downstream targets, certainly of bound and regulated miRNAs revealed the associated function between the master regulator FoxP3 and miRNAs as regulators itself. miR-155 is shown to be crucially involved in nTreg cell mediated tolerance by regulating the susceptibility of conventional human as well as murine CD4(+) Th cells to nTreg cell-mediated suppression

Human CD4 CD25 regulatory T cells : proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function

CD4( )CD25( )Foxp3( ) regulatory T cells (CD25( ) Treg cells) direct the maintenance of immunological self-tolerance by active suppression of autoaggressive T-cell populations. However, the molecules mediating the anergic state and regulatory function of CD25( ) Treg cells are still elusive. Using differential proteomics, we identified galectin-10, a member of the lectin family, as constitutively expressed in human CD25( ) Treg cells, while they are nearly absent in resting and activated CD4( ) T cells. These data were confirmed on the mRNA and protein levels. Single-cell staining and flow cytometry showed a strictly intracellular expression of galectin-10 in CD25( ) Treg cells. Specific inhibition of galectin-10 restored the proliferative capacity of CD25( ) Treg cells and abrogated their suppressive function. Notably, first identified here as expressed in human T lymphocytes, galectin-10 is essential for the functional properties of CD25( ) Treg cells

miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression

BACKGROUND: In humans and mice naturally occurring CD4( )CD25( ) regulatory T cells (nTregs) are a thymus-derived subset of T cells, crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Recent work using Dicer-deficient mice irrevocably demonstrated the importance of miRNAs for nTreg cell-mediated tolerance. PRINCIPAL FINDINGS: DNA-Microarray analyses of human as well as murine conventional CD4( ) Th cells and nTregs revealed a strong up-regulation of mature miR-155 (microRNA-155) upon activation in both populations. Studying miR-155 expression in FoxP3-deficient scurfy mice and performing FoxP3 ChIP-Seq experiments using activated human T lymphocytes, we show that the expression and maturation of miR-155 seem to be not necessarily regulated by FoxP3. In order to address the functional relevance of elevated miR-155 levels, we transfected miR-155 inhibitors or mature miR-155 RNAs into freshly-isolated human and mouse primary CD4( ) Th cells and nTregs and investigated the resulting phenotype in nTreg suppression assays. Whereas miR-155 inhibition in conventional CD4( ) Th cells strengthened nTreg cell-mediated suppression, overexpression of mature miR-155 rendered these cells unresponsive to nTreg cell-mediated suppression. CONCLUSION: Investigation of FoxP3 downstream targets, certainly of bound and regulated miRNAs revealed the associated function between the master regulator FoxP3 and miRNAs as regulators itself. miR-155 is shown to be crucially involved in nTreg cell mediated tolerance by regulating the susceptibility of conventional human as well as murine CD4( ) Th cells to nTreg cell-mediated suppression