Plasmacytoid dendritic cells (pDCs) are a specialized DC subset mainly associated with sensing viral pathogens and high-type I interferon (IFN-I) release in response to toll-like receptor (TLR)-7 and ...TLR-9 signaling. Currently, pDC contribution to inflammatory responses is extensively described; nevertheless, their regulatory mechanisms require further investigation. CD39 and CD73 are ectoenzymes driving a shift from an ATP-proinflammatory milieu to an anti-inflammatory environment by converting ATP to adenosine. Although the regulatory function of the purinergic halo CD39/CD73 has been reported in some immune cells like regulatory T cells and conventional DCs, its presence in pDCs has not been examined. In this study, we uncover for the first time the expression and functionality of the purinergic halo in human blood pDCs. In healthy donors, CD39 was expressed in the cell surface of 14.0 ± 12.5% pDCs under steady-state conditions, while CD73 showed an intracellular location and was only expressed in 8.0 ± 2.2% of pDCs. Nevertheless, pDCs stimulation with a TLR-7 agonist (R848) induced increased surface expression of both molecules (43.3 ± 23.7% and 18.6 ± 9.3%, respectively), as well as high IFN-α secretion. Furthermore, exogenous ATP addition to R848-activated pDCs significantly increased adenosine generation. This effect was attributable to the superior CD73 expression and activity because blocking CD73 reduced adenosine production and improved pDC allostimulatory capabilities on CD4 + T cells. The functional expression of the purinergic halo in human pDCs described in this work opens new areas to investigate its participation in the regulatory pDC mechanisms in health and disease.
The proliferation and survival of malignant B cells in chronic lymphocytic leukemia (CLL) depend on signals from the microenvironment in lymphoid tissues. Among a plethora of soluble factors, IL-8 ...has been considered one of the most relevant to support CLL B cell progression in an autocrine fashion, even though the expression of IL-8 receptors, CXCR1 and CXCR2, on leukemic B cells has not been reported. Here we show that circulating CLL B cells neither express CXCR1 or CXCR2 nor they respond to exogenous IL-8 when cultured in vitro alone or in the presence of monocytes/nurse-like cells. By intracellular staining and ELISA we show that highly purified CLL B cells do not produce IL-8 spontaneously or upon activation through the B cell receptor. By contrast, we found that a minor proportion (<0.5%) of contaminating monocytes in enriched suspensions of leukemic cells might be the actual source of IL-8 due to their strong capacity to release this cytokine. Altogether our results indicate that CLL B cells are not able to secrete or respond to IL-8 and highlight the importance of methodological details in in vitro experiments.
To determine the pregnancy outcome as a function of the first-trimester serum 25-hydroxyvitamin D
3 25(OH)D status and to compare the 25(OH)D levels in the first and third trimesters.
Pregnant women ...(n
=
466) tested for serum 25(OH)D levels during the first trimester were followed up until the end of pregnancy, and the obstetric and neonatal outcomes were compared in reference to the baseline 25(OH)D status. The third-trimester 25(OH)D levels were additionally measured in a subset of women (n
=
148).
The obstetric and neonatal outcomes did not vary as a function of the first-trimester 25(OH)D status. Neither did the 25(OH)D levels vary as a function of pregnancy outcomes. Overall, the 25(OH)D levels significantly decreased from the first to the third trimester. The first- and third-trimester 25(OH)D levels of samples initially taken during autumn/winter were significantly lower than those that were initially taken during spring/summer. Interestingly, the decrease in 25(OH)D levels during the third trimester was independent of the season of sampling.
The pregnancy outcome was independent of the first-trimester 25(OH)D status. Overall, the 25(OH)D levels significantly decreased in the third trimester. More research in this area is warranted.
This paper presents an analysis of the correlation effect in the uncertainty estimation of a system for humidity generation based on the two pressures principle. In order to compare the validity of ...the calculations, two methods for evaluating uncertainty, including the correlation between the input variables, were used. The first one was the classical approximation based on the applicability of the central limit theorem, while the second consisted of the propagation of the input distributions using Monte Carlo simulations. The obtained results show that the usual assumption of negligible correlations between the input variables is valid for uncertainty levels in calibrations of hygrometers.
Dysferlinopathy encompasses a group of rare muscular dystrophies caused by recessive mutations in the DYSF gene. The phenotype ranges from asymptomatic elevated serum creatine kinase (hyperCKemia) to ...selective and progressive involvement of the proximal and/or distal muscles of the limbs. Bohan and Peter criteria are the most widely used for the diagnosis of polymyositis, but they have limitations and can misclassify muscular dystrophies with inflammation as polymyositis. Most dysferlinopathy patients have muscle biopsies with inflammation and thus are vulnerable to misdiagnosis with polymyositis and inappropriate treatment with steroids and immunosuppressors. We report a dysferlinopathy patient who was misdiagnosed with juvenile polymyositis and explore in a literature review how common such misdiagnoses are. With diagnosis based only on routine clinicopathological examinations, distinguishing an inflammatory myopathy from dysferlinopathy is quite difficult. We suggest that before establishing a diagnosis of "definite" or "probable" juvenile polymyositis, according to Bohan and Peter or current ACR/EULAR criteria, a muscular dystrophy must first be ruled out.
Because of their plasticity and central role in orchestrating immunity and tolerance, DCs can respond to pregnancy‐specific signals, thus promoting the appropriate immune response in order to support ...pregnancy. Here, we show that pregnancy‐specific glycoprotein (PSG1a), the major variant of PSG released into the circulation during pregnancy, targets DCs to differentiate into a subset with a unique phenotype and function. This semi‐mature phenotype is able to secrete IL‐6 and TGF‐β. PSG1a also affected the maturation of DCs, preventing the up‐regulation of some costimulatory molecules, and inducing the secretion of TGF‐β or IL‐10 and the expression of programmed death ligand 1 (PD‐L1) in response to TLR‐9 or CD40 ligation. In addition, PSG1a‐treated DCs promoted the enrichment of Th2‐type cytokines, IL‐17‐producing cells, and Treg cells from CD4+ T cells from DO11.10 Tg mice. Moreover, in vivo expression of PSG1a promoted the expansion of Ag‐specific CD4+CD25+Foxp3+ Treg cells and IL‐17‐, IL‐4‐, IL‐5‐, and IL‐10‐secreting cells able to protect against Listeria monocytogenes infection. Taken together, our data indicate that DCs can be targeted by PSG1a to generate the signals necessary to mount an appropriate, well‐balanced, and effective immune response able to protect against invading pathogens while at the same time being compatible with a successful pregnancy.
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