Exploring Species-Specificity in TLR4/MD-2 Inhibition with Amphiphilic Lipid A Mimicking Glycolipids.

The Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex is a key receptor of the innate immune system and a major driver of inflammation that is responsible for the multifaceted defense response to Gram-negative infections. However, dysfunction in the tightly regulated mechanisms of TLR4-mediated signaling leads to the uncontrolled upregulation of local and systemic inflammation, often resulting in acute or chronic disease. Therefore, the TLR4/MD-2 receptor complex is an attractive target for the design and development of anti-inflammatory therapies which aim to control the unrestrained activation of TLR4-mediated signaling.

Microenvironmental and cell intrinsic factors governing human cDC2 differentiation and monocyte reprogramming.

cDC2s occur abundantly in peripheral tissues and arise from circulating blood cDC2s. However, the factors governing cDC2 differentiation in tissues, especially under inflammatory conditions, remained poorly defined. We here found that psoriatic cDC2s express the efferocytosis receptor Axl and exhibit a bone morphogenetic protein (BMP) and p38MAPK signaling signature.

A novel 3D cell culture model to study the human small intestinal immune landscape.

Several subsets of mononuclear phagocytes and DCs (MDC) populate the small intestine (SI), and these cells reportedly exert specialized functions in anti-microbial immunity and tolerance. Given the specialized phenotype of these cells, differing from other MDC family members, including their putative circulating blood precursors, local intestinal factors play key instructive roles in their differentiation. We designed an SI cell culture model composed of three intestinal epithelial cell (IEC) types, including absorptive enterocytes (E cells), antigen delivering microfold (M) cells, and mucus-producing goblet (G) cells plus T lymphocytes and soluble B cell-derived factors.

Immunomodulatory Effects of Aronia Juice Polyphenols-Results of a Randomized Placebo-Controlled Human Intervention Study and Cell Culture Experiments.

Dietary polyphenols, which are present in have been associated with various beneficial effects on human health including antioxidant, antiviral, and anti-inflammatory activities. We aimed to investigate the immunomodulatory effects of aronia juice polyphenols in a randomized placebo-controlled human intervention study and cell culture experiments. A total of 40 females were asked to consume either 200 mL of aronia juice or a placebo drink for six weeks and were investigated again after a washout period of another six weeks.

The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling.

Transforming growth factor β (TGF-β) family ligands are key regulators of dendritic cell (DC) differentiation and activation. Epidermal Langerhans cells (LCs) require TGF-β family signaling for their differentiation, and canonical TGF-β1 signaling secures a non-activated LC state. LCs reportedly control skin inflammation and are replenished from peripheral blood monocytes, which also give rise to pro-inflammatory monocyte-derived DCs (moDCs).

Bone morphogenetic protein signaling regulates skin inflammation via modulating dendritic cell function.

Background: Bone morphogenetic proteins (BMPs) are members of the TGF-β family that signal via the BMP receptor (BMPR) signaling cascade, distinct from canonical TGF-β signaling. BMP downstream signaling is strongly induced within epidermal keratinocytes in cutaneous psoriatic lesions, and BMP7 instructs monocytic cells to acquire characteristics of psoriasis-associated Langerhans dendritic cells (DCs). Regulatory T (Treg)-cell numbers strongly increase during psoriatic skin inflammation and were recently shown to limit psoriatic skin inflammation.

miR-181a Modulation of ERK-MAPK Signaling Sustains DC-SIGN Expression and Limits Activation of Monocyte-Derived Dendritic Cells.

DC-SIGN monocyte-derived dendritic cells (mo-DCs) play important roles in bacterial infections and inflammatory diseases, but the factors regulating their differentiation and proinflammatory status remain poorly defined. Here, we identify a microRNA, miR-181a, and a molecular mechanism that simultaneously regulate the acquisition of DC-SIGN expression and the activation state of DC-SIGN mo-DCs. Specifically, we show that miR-181a promotes DC-SIGN expression during terminal mo-DC differentiation and limits its sensitivity and responsiveness to TLR triggering and CD40 ligation.

BMP7 aberrantly induced in the psoriatic epidermis instructs inflammation-associated Langerhans cells.

Background: Epidermal hyperplasia represents a morphologic hallmark of psoriatic skin lesions. Langerhans cells (LCs) in the psoriatic epidermis engage with keratinocytes (KCs) in tight physical interactions; moreover, they induce T-cell-mediated immune responses critical to psoriasis.

Objective: This study sought to improve the understanding of epidermal factors in psoriasis pathogenesis.

The avian chorioallantoic membrane as an alternative tool to study medullary thyroid cancer.

Preclinical trials of medullary thyroid cancer (MTC) therapeutics require both in vitro and in vivo analyses. Human tumour xenografted rodent models, which are considered the 'gold standard' to study and validate the efficacy and toxicity of lead compounds before translation to clinical trials, are very expensive, subject to organismal variability and ethical controversies. The avian chorioallantoic membrane (CAM) assay provides an alternative versatile, cost-effective and ethically less objectionable short-term, in vivo model for reliable screening of drugs.