The selective vitamin D receptor agonist, elocalcitol, reduces endometriosis development in a mouse model by inhibiting peritoneal inflammation.

Background: Endometriosis, which is characterized by the growth of endometrial tissue at ectopic locations as well as vascular development and inflammation, is still an unmet clinical need since an optimal drug that allows for both pain and infertility management does not exist. Since both the eutopic and the ectopic endometrium express the vitamin D receptor (VDR), and VDR agonists are endowed with anti-proliferative and anti-inflammatory properties, we evaluated the effect of elocalcitol, a VDR agonist with low calcaemic liability, in a mouse model of experimentally induced endometriosis.

Methods And Results: Endometriosis was induced by injection of syngeneic endometrial tissue fragments into adult Balb/c female mice.

Macrophages are alternatively activated in patients with endometriosis and required for growth and vascularization of lesions in a mouse model of disease.

The mechanisms that sustain endometrial tissues at ectopic sites in patients with endometriosis are poorly understood. Various leukocytes, including macrophages, infiltrate endometriotic lesions. In this study, we depleted mouse macrophages by means of either clodronate liposomes or monoclonal antibodies before the injection of syngeneic endometrial tissue.

Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis.

Triggering receptor expressed on myeloid cells (TREM-2) is a membrane receptor associated with DAP12 that is expressed primarily in myeloid cells, including dendritic cells and microglia, and promotes fusion of osteoclast precursors into multinucleated cells. A rare autosomal recessive condition, Nasu-Hakola disease (NHD) is associated with loss-of-function mutations in DAP12 and TREM-2. The brain pathology observed in NHD patients suggests that disruption of the TREM-2/DAP12 pathway leads to neurodegeneration with demyelination and axonal loss.

CC chemokine receptor expression in childhood asthma is influenced by natural allergen exposure.

Chemokines and their receptors may play an important role for leukocyte trafficking in allergic inflammation. Aim was to evaluate whether expression of chemokine receptors CCR4 and CCR8 on cells obtained by sputum induction from asthmatic allergic children may be influenced by house dust mite (HDM) allergen natural exposure. Twenty-one children (7-13 yr) with moderate asthma and sensitized to HDM were evaluated during a prolonged period of allergen avoidance (T0) and after a period of natural allergen exposure (T1).

Chemokine receptors in chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is a debilitating disease characterized by recurrent episodes of leukocyte infiltration in the lung parenchyma causing progressive pulmonary tissue damage and loss of function. Recruitment of neutrophils and CD8+ T cells is linked to disease progression and is under control of chemotactic mediators produced in the inflamed COPD lung. Recent progress in elucidation of the molecular mechanisms that regulate migration of inflammatory cells into the lung has revealed interesting novel targets for therapeutic intervention in this disease.

Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia.

Together with its adaptor protein, the adaptor protein of 12 kDa also known as KARAP and TYROBP (DAP12), triggering receptor expressed in myeloid cells 2 (TREM2) is a stimulatory membrane receptor of the immunoglobulin/lectin-like superfamily, well known in myeloid cells. In humans, however, loss-of-function mutations of TREM2/DAP12 leave myeloid cells unaffected but induce an autosomal recessive disease characterized, together with bone cysts, by a spectrum of pathological lesions in the cortex, thalamus and basal ganglia with clinical symptoms of progressive dementia (polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy). Nothing was known about the role of TREM2/DAP12 in brain cell biology and physiology.

Production of profibrotic cytokines by invariant NKT cells characterizes cirrhosis progression in chronic viral hepatitis.

Invariant (inv)NKT cells are a subset of autoreactive lymphocytes that recognize endogenous lipid ligands presented by CD1d, and are suspected to regulate the host response to cell stress and tissue damage via the prompt production of cytokines. We investigated invNKT cell response during the progression of chronic viral hepatitis caused by hepatitis B or C virus infection, a major human disease characterized by a diffused hepatic necroinflammation with scarring fibrotic reaction, which can progress toward cirrhosis and cancer. Ex vivo frequency and cytokine production were determined in circulating and intrahepatic invNKT cells from controls (healthy subjects or patients with nonviral benign or malignant focal liver damage and minimal inflammatory response) or chronic viral hepatitis patients without cirrhosis, with cirrhosis, or with cirrhosis and hepatocellular carcinoma.

Dominance of CCL22 over CCL17 in induction of chemokine receptor CCR4 desensitization and internalization on human Th2 cells.

Chemokines and their receptors play a pivotal role in controlling T cell trafficking in immunity and inflammation. Two chemokines, CCL17 and CCL22, activate the chemokine receptor CCR4, expressed on functionally distinct subsets of T cells: cutaneous leukocyte-associated antigen (CLA)+ skin-homing, T helper (Th) 2, and CD25+ T suppressor cells. Here, we compared the ability of CCL17 and CCL22 to promote CCR4 internalization as a mechanism of regulation of receptor function on human Th2 cells.

Analysis of homing receptor expression on infiltrating leukocytes in disease states.

Chemokines represent a large family of polypeptides that signal through G-protein-coupled receptors and have a role in chemotaxis, leukocyte homing, inflammation, hematopoiesis, angiogenesis and tumor growth. The chemokine/chemokine receptor system acts in coordination with a complex cytokine network to elicit and direct leukocyte infiltration into the inflamed tissue. In addition to promoting movement into the inflamed tissue, the chemokine/chemokine receptor system may also activate infiltrating cells, such as neutrophils and eosinophils, and induce local damage.

Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease.

CXCR3 is a chemokine receptor preferentially expressed on lymphocytes, particularly on type-1 T-lymphocytes. Smokers who develop chronic obstructive pulmonary disease (COPD) have a chronic bronchopulmonary inflammation that is characterized by an increased infiltration of T-lymphocytes, particularly CD8(+), in the airways and lung parenchyma. To investigate the expression of CXCR3 and its ligand interferon-induced protein 10/CXCL10 in COPD, we counted the number of CXCR3(+) cells and analyzed the expression of CXCL10 in the peripheral airways of 19 patients undergoing lung resection for localized pulmonary lesions.