Transglutaminase 2 (TG2) is a multifunctional protein that promotes clearance of apoptotic cells (efferocytosis) acting as integrin β₃ coreceptor. Accumulating evidence indicates that defective efferocytosis contributes to the development of chronic inflammatory diseases. Obesity is characterized by the accumulation of dead adipocytes and inflammatory macrophages in the adipose tissue leading to obesity-related metabolic syndrome. Here, we report that loss of TG2 from bone marrow-derived cells sensitizes for high fat diet (HFD)-induced pathologies. We find that metabolically activated TG2 null macrophages express more phospho-Src and integrin β₃, unexpectedly clear dying adipocytes more efficiently via lysosomal exocytosis, but produce more pro-inflammatory cytokines than the wild type ones. Anti-inflammatory treatment with an LXR agonist reverts the HFD-induced phenotype in mice lacking TG2 in bone marrow-derived cells with less hepatic steatosis than in wild type mice proving enhanced lipid clearance. Thus it is interesting to speculate whether LXR agonist treatment together with enhancing lysosomal exocytosis could be a beneficial therapeutic strategy in obesity.

Background. Systemic sclerosis is an autoimmune disease, characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. Changes in levels of proangiogenic cytokines had already been determined largely in serum. Our aim was to assess the levels of VEGF in human tears of patients with SSC. Patients and methods. Forty‐three patients (40 female and 3 men, mean (SD) age 61 (48–74) years) with SSc and 27 healthy controls were enrolled in this study. Basal tear sample collection and tear velocity investigations were carried out followed by an ophthalmological examination. Total protein concentrations and VEGF levels were determined in tear samples. Results. The average collected tear fluid volume developed 10.4 μL (1.6–31.2) in patients and 15.63 μL (3.68–34.5) in control subjects. The average total protein level was 6.9 μg/μL (1.8–12.3) in tears of patients and control tears contained an average of 4.132 μg/μL (0.1–14.1) protein. In patients with SSc the average concentration of VEGF was 4.9 pg/μL (3.5–8.1) and 6.15 pg/μL (3.84–12.3) in healthy samples. Conclusions. Total protein production was increased because of the smaller tear volume. Decreased VEGF in tear of SSc patients can be explained also by the decreased tear secretion of patients.

Obesity is characterized by low-grade inflammation that originates predominantly from the expanding visceral adipose tissue, in which adipocytes respond to lipid overload with hypertrophy, and consequently die by apoptosis. Recruited adipose tissue macrophages (ATMs) take up the excess lipids and remove the dead cells; however, long-term exposure to high concentrations of lipids alters their phenotype to M1-like ATMs that produce pro-inflammatory cytokines and resistin leading to insulin resistance and other obesity-related pathologies. Mer tyrosine kinase is expressed by macrophages and by being an efferocytosis receptor, and by suppressing inflammation, we hypothesized that it might play a protective role against obesity. To our surprise, however, the loss of Mer protected mice against high-fat diet (HFD)-induced obesity. We report in this paper that Mer is also expressed by adipocytes of both white and brown adipose tissues, and while its activity facilitates adipocyte lipid storage both in vitro and in vivo in mice exposed to HFD, it simultaneously attenuates thermogenesis in the brown adipose tissue contributing to its ‘whitening’. Our data indicate that Mer is one of the adipocyte tyrosine kinase receptors, the activity of which contributes to the metabolic decision about the fate of excess lipids favoring their storage within the body.

Background Systemic sclerosis (SSc) is an autoimmune disease, characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. SSc may be associated with sicca syndrome. Changes in levels of proangiogenic and proinflammatory cytokines had already been determined largely in serum, however, the local inflammatory and cytokine milieu in the tear of SSc patients has not yet been evaluated. Objectives We wished to determine VEGF and other cytokine and chemokine levels in tear samples of SSc patients. Methods First, forty-three patients (40 female and 3 men, mean (SD) age 61 (48–74) years) with SSc and 27 healthy controls were enrolled in the VEGF study. Basal tear sample collection and tear velocity investigations were carried out followed by an ophthalmological examination. Total protein concentrations and VEGF levels were determined in tear samples. In the multiple cytokine study, unstimulated tear samples were collected from nine patients with SSc and 12 age- and gender-matched healthy controls. The relative levels of 102 different cytokines were determined by a cytokine array, and then absolute levels of four key cytokines were determined by a magnetic bead assay. Results In the first study, the mean collected tear fluid volume developed 10.4 L (1.6–31.2) in patients and 15.63 L (3.68–34.5) in control subjects. The mean total protein level was 6.9 g/L (1.8–12.3) and 4.1 g/L (0.1–14.1) in tear samples of SSc patients and controls, respectively. In patients with SSc, the mean VEGF tear concentration was 4.9 pg/L (3.5–8.1) compared to 6.15 pg/L (3.84–12.3) in healthy samples. Multicytokine-array studies revealed shifted cytokine profile characterized by predominance of proinflammatory mediators in the tear samples of SSc patients. Out of the 102 analyzed proteins, nine were significantly increased in tears of patients with SSc. Based on the multiplex bead results, CRP, interferon-inducible protein 10 (IP-10) and monocyte chemoattractant protein-1 (mcp-1) levels were significantly higher in tears of patients with SSc compared to controls. Conclusions Impaired angiogenesis has been found by other investigators in SSc. This is reflected by lower VEGF levels in the tear samples of SSc patients compared to controls. The multi-cytokine array study revealed increased production of CRP and two important pro-inflammatory chemokines in the tear of SSc patients. Our current data depict a group of inflammatory mediators, which may play a significant role in ocular pathology of SSc. Disclosure of Interest None declared