Human plasmacytoid dendritic cells express the functional purinergic halo (CD39/CD73).

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.

Liver damage in bleomycin-induced pulmonary fibrosis in mice.

Pulmonary fibrosis is an emerging disease with a poor prognosis and high mortality rate that is even surpassing some types of cancer. This disease has been linked to the concomitant appearance of liver cirrhosis. Bleomycin-induced pulmonary fibrosis is a widely used mouse model that mimics the histopathological and biochemical features of human systemic sclerosis, an autoimmune disease that is associated with inflammation and expressed in several corporal systems as fibrosis or other alterations. To determine the effects on proliferation, redox and inflammation protein expression markers were analyzed by immunohistochemistry. Analyses showed a significant increase in protein oxidation levels by lipoperoxidation bio-products and in proliferation and inflammation processes. These phenomena were associated with the induction of the redox status in mice subjected to 100 U/kg bleomycin. These findings clearly show that the bleomycin model induces histopathological alterations in the liver and partially reproduces the complexity of systemic sclerosis. Our results using the bleomycin-induced pulmonary fibrosis model provide a protocol to investigate the mechanism underlying the molecular alteration found in the liver linked to systemic sclerosis.

Distrés psíquico en el ámbito hospitalario / Psychic distress in hospital setting

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Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8alpha(-) and CD8alpha(+) dendritic cells are generated from CD4(low) lymphoid-committed precursors.

Two dendritic cell (DC) subsets have been identified in the murine system on the basis of their differential CD8alpha expression. CD8alpha(+) DCs and CD8alpha(-) DCs are considered as lymphoid- and myeloid-derived, respectively, because CD8alpha(+) but not CD8alpha(-) splenic DCs were generated from lymphoid CD4(low) precursors, devoid of myeloid reconstitution potential. Although CD8alpha(-) DCs were first described as negative for CD4, our results demonstrate that approximately 70% of them are CD4(+). Besides CD4(-) CD8alpha(-) and CD4(+) CD8alpha(-) DCs displayed a similar phenotype and T-cell stimulatory potential in mixed lymphocyte reaction (MLR), although among CD8alpha(-) DCs, the CD4(+) subset appears to have a higher endocytic capacity. Finally, experiments of DC reconstitution after irradiation in which, in contrast to previous studies, donor-type DCs were analyzed without depleting CD4(+) cells, revealed that both CD8alpha(+) DCs and CD8alpha(-) DCs were generated after transfer of CD4(low) precursors. These data suggest that both CD8alpha(+) and CD8alpha(-) DCs derive from a common precursor and, hence, do not support the concept of the CD8alpha(+) lymphoid-derived and CD8alpha(-) myeloid-derived DC lineages. However, because this hypothesis has to be confirmed at the clonal level, it remains possible that CD8alpha(-) DCs arise from a myeloid precursor within the CD4(low) precursor population or, alternatively, that both CD8alpha(+) and CD8alpha(-) DCs derive from an independent nonlymphoid, nonmyeloid DC precursor. In conclusion, although we favor the hypothesis that both CD8alpha(+) and CD8alpha(-) DCs derive from a lymphoid-committed precursor, a precise study of the differentiation process of CD8alpha(+) and CD8alpha(-) DCs is required to define conclusively their origin.