Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB-induced Bcl-xL for inhibition of apoptosis.

Eosinophils are associated with type 2 immune responses to allergens and helminths. They release various proinflammatory mediators and toxic proteins on activation and are therefore considered proinflammatory effector cells. Eosinophilia is promoted by the cytokines interleukin (IL)-3, IL-5, and granulocyte macrophage-colony-stimulating factor (GM-CSF) and can result from enhanced de novo production or reduced apoptosis.

Primary cutaneous follicle center lymphoma with diffuse CD30 expression: a report of 4 cases of a rare variant.

Background: CD30 is expressed in aggressive and Epstein-Barr virus-associated forms of B-cell non-Hodgkin lymphomas, but is rarely expressed by the majority of tumor cells in primary cutaneous B-cell lymphomas (CBCLs). The expression of CD30 in CBCLs may be at risk for misinterpretation as an unequivocal indicator of a highly aggressive form of the disease.

Objective: We report 4 cases of low malignant primary cutaneous follicle center lymphoma (PCFCL) with diffuse and strong expression of CD30 by the majority of neoplastic cells.

Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties.

Cell-type plasticity within a tumor has recently been suggested to cause a bidirectional conversion between tumor-initiating stem cells and nonstem cells triggered by an inflammatory stroma. NF-κB represents a key transcription factor within the inflammatory tumor microenvironment. However, NF-κB's function in tumor-initiating cells has not been examined yet.

Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells.

Fumarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4-producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23.

Myeloid IκBα deficiency promotes atherogenesis by enhancing leukocyte recruitment to the plaques.

Activation of the transcription factor NF-κB appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-κB inhibitor IκBα in atherosclerosis. Myeloid-specific deletion of IκBα results in larger and more advanced lesions in LDL-R-deficient mice without affecting the compositional phenotype of the plaques or systemic inflammatory markers in the plasma.

What is really in control of skin immunity: lymphocytes, dendritic cells, or keratinocytes? facts and controversies.

The pathophysiology of atopic dermatitis is still under discussion. Although it is widely accepted that environmental factors and a genetic predisposition are essential, the role of the innate and adaptive immune system and the functional cascade of the cells involved is still unclear. A concept that integrates all immune cells as equally essential has allure.

Complementary therapy for atopic dermatitis and other allergic skin diseases: facts and controversies.

The term complementary or alternative medicine encompasses numerous diverse therapeutic concepts, ranging from as herbal medicine, diet with essential fatty acids, and probiotics, to acupuncture. The main focus of these treatment methods is inflammatory skin disease, in particular atopic dermatitis. Although integrative medicine enjoys increasing popularity, particularly in industrialized countries, clinical studies that meet the double-blind, placebo-controlled standard are rare or nonexistent.

The potential role of c-Jun activation in patients with cutaneous lichen planus.

c-Jun, a component of the activating protein-1 transcription factor family, has been known to play an important role in the control of cell proliferation. It is also suspected to be a critical mediator of tumor promotion. However, investigations of c-Jun activation patterns in inflammatory and inflammatory transforming skin diseases have not been described so far.

IkappaBalpha is required for marginal zone B cell lineage development.

Inactivation of members of the nuclear factor-kappaB (NF-kappaB) family results in the decrease or defect of marginal zone B (MZB) cells. It is not known which inhibitors of the NF-kappaB family (IkappaB) are required for MZB cell development. Here, we show that mice with B cell-specific inactivation of the main NF-kappaB inhibitor IkappaBalpha have a marked decrease of MZB cells and their presumed precursors.

Role of NF-kappaB/RelA and MAPK pathways in keratinocytes in response to sulfur mustard.

Sulfur mustard (SM) is a strong vesicant that has been used as a chemical warfare agent. To understand the molecular mechanisms that underlie the inflammatory skin reaction in response to SM, we analyzed the activation pattern of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways. Keratinocytes responded with an induction of the canonical NF-kappaB pathway, including activation of IkappaB kinase 2, followed by phosphorylation and degradation of IkappaBalpha and of the transactivating subunit RelA at Ser536.

Crosstalk between keratinocytes and adaptive immune cells in an IkappaBalpha protein-mediated inflammatory disease of the skin.

Inflammatory diseases at epithelial borders develop from aberrant interactions between resident cells of the tissue and invading immunocytes. Here, we unraveled basic functions of epithelial cells and immune cells and the sequence of their interactions in an inflammatory skin disease. Ubiquitous deficiency of the IkappaBalpha protein (Ikba(Delta)(/Delta)) as well as concomitant deletion of Ikba specifically in keratinocytes and T cells (Ikba(K5Delta/K5Delta lckDelta/lckDelta)) resulted in an inflammatory skin phenotype that involved the epithelial compartment and depended on the presence of lymphocytes as well as tumor necrosis factor and lymphotoxin signaling.

Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation.

Psoriasis is a common skin disease, the pathogenesis of which has not yet been resolved. In mice, epidermis-specific deletion of inhibitor of NF-kappaB (IkappaB) kinase 2 (IKK2) results in a skin phenotype that mimics human psoriasis in several aspects. Like psoriasis, this skin disease shows pronounced improvement when mice are treated with a TNF-neutralizing agent.

[Graft-versus-host disease: a dermatologic view of an interdisciplinary problem].

Graft-versus-host disease (GVHD) is a frequent complication following hematopoietic stem cell transplantation. Acute and chronic GVHD are identified based on the onset of clinical symptoms and signs. Whereas acute GVHD is relatively uniform in its appearance, chronic GVHD is characterized by a broad spectrum of clinical manifestations.

Stroma-mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha.

Hematopoiesis occurs in the liver and the bone marrow (BM) during murine development. Newborn mice with a ubiquitous deletion of I kappa B alpha develop a severe hematological disorder characterized by an increase of granulocyte/erythroid/monocyte/macrophage colony-forming units (CFU-GEMM) and hypergranulopoiesis. Here, we report that this particular myeloproliferative disturbance is mediated by continuously deregulated perinatal expression of Jagged1 in I kappa B alpha-deficient hepatocytes.

Toll-like receptors as key mediators in innate antifungal immunity.

The Toll protein of Drosophila is a transmembrane receptor involved in dorsoventral polarization during embryonic development and recognition of infection. In mammals, Toll-like receptors (TLRs) constitute a novel protein family involved in innate immunity and respond to a wide spectrum of microorganisms, including fungi, bacteria, viruses, and protozoa. Specific agonists for nine of the ten members of the human TLR family have been described to date.

Induction of nuclear factor- kappa B and c-Jun/activator protein-1 via toll-like receptor 2 in macrophages by antimycotic-treated Candida albicans.

We examined the role of Toll-like receptors (TLRs) by using TLR2-deficient (TLR2(-/-)), TLR4-defective (TLR4(d/d)), and double-knockout murine macrophages and human embryonic kidney (HEK) 293 cells transfected with human TLR2 or TLR4 expression plasmids after stimulation with different preparations of the human pathogenic fungus Candida albicans. Compared with wild-type macrophages, TLR2(-/-) and TLR4(d/d) macrophages had impaired recognition of viable C. albicans, whereas antimycotic (AM)-treated C.

Toll-like receptors and innate antifungal responses.

The mammalian Toll-like receptors (TLRs) are homologues of Drosophila Toll and constitute a novel protein family involved in the mediation of innate immunity and the activation of adaptive immunity. Analysis of infection with human pathogenic fungi Candida albicans and Aspergillus fumigatus implicated TLR2 and TLR4 in elicitation of immune responses. Cryptococcus neoformans is recognized by a process that uses TLR4.

Inactivation of the F4/80 glycoprotein in the mouse germ line.

Macrophages play a crucial role in the defense against pathogens. Distinct macrophage populations can be defined by the expression of restricted cell surface proteins. Resident tissue macrophages, encompassing Kupffer cells of the liver and red pulp macrophages of the spleen, characteristically express the F4/80 molecule, a cell surface glycoprotein related to the seven transmembrane-spanning family of hormone receptors.

Aggregation of the high-affinity IgE receptor Fc(epsilon)RI on human monocytes and dendritic cells induces NF-kappaB activation.

In contrast to mast cells and basophils, the high-affinity IgE receptor (Fc(epsilon)RI) on monocytes and dendritic cells (DC), including epidermal Langerhans cells, is not constitutively expressed and lacks the beta-chain. Fc(epsilon)RI is upregulated on Langerhans cells of atopic individuals, particularly in atopic dermatitis skin. Although Fc(epsilon)RI provides IgE-mediated antigen focusing on monocytes and DC/Langerhans cells, its relevance for cell activation remains elusive, and the transcription factors regulating Fc(epsilon)RI-induced genes are unknown.