Immunology Area

Rome, Italy

Immunology Area

Rome, Italy
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Pistoia V.,Immunology Area | Raffaghello L.,Instituto Giannina Gaslini
International Immunology | Year: 2017

Mesenchymal stromal cells (MSCs) are committed progenitors of mesodermal origin that are found virtually in every organ and exhibit multilineage differentiation into osteocytes, adipocytes and chondrocytes. MSCs also mediate a wide spectrum of immunoregulatory activities that usually dampen innate and adaptive immune responses. These features have attracted interest in the perspective of developing novel cell therapies for autoimmune disease. However, depending on the microenvironmental conditions, MSCs may show a plastic behavior and switch to an immunostimulatory phenotype. After thorough characterization of the effects of MSCs on the immune system, MSC cell therapy has been tested in animal models of autoimmunity using different cell sources, protocols of in vitro expansion and routes and schedules of administration. The pre-clinical results have been encouraging in some models [e.g. Crohn's disease (CD), multiple sclerosis] and heterogeneous in others (e.g. graft-versus-host disease, systemic lupus erythematosus, rheumatoid arthritis). Clinical trials have been carried out and many are ongoing. As discussed, the results obtained are too preliminary to draw any conclusion, with the only exception of topical administration of MSCs in CD that has proven efficacious. The mechanism of action of infused MSCs is still under investigation, but the apparent paradox of a therapeutic effect achieved in spite of the very low number of cells reaching the target organ has been solved by the finding that MSC-derived extracellular vesicles (EVs) closely mimic the therapeutic activity of MSCs in pre-clinical models. These issues are critically discussed in view of the potential clinical use of MSC-derived EVs. © The Japanese Society for Immunology. 2017.


Bason C.,University of Verona | Pagnini I.,University of Florence | Brucato A.,Internal Medicine | Maestroni S.,Internal Medicine | And 3 more authors.
Lupus | Year: 2017

Immune-mediated sensorineural hearing loss may complicate systemic autoimmune diseases. We have previously reported the presence of antibodies directed against inner ear antigens in patients with Cogan syndrome, a disease characterized by sudden hearing loss and interstitial keratitis. Such autoantibodies cross-react with an epitope of SSA/Ro60 protein. Anti-Ro/SSA antibodies in pregnant women cross the placenta and reach the fetal tissues inducing an immune-mediated damage of the cardiac conduction system. We wanted to evaluate whether mothers with anti-Ro/SSA antibodies who gave birth to children with congenital heart block have antibodies directed against inner ear antigens and whether these antibodies are connected with the presence of immune-mediated sensorineural hearing loss. We did not find anti-inner ear antibodies in the majority of the mothers. On the contrary a 13-year-old boy with congenital heart block and sensorineural hearing loss was positive for the presence of anti-inner ear antigens antibodies. Moreover his serum was positive for the presence of anti-Ro60 peptide antibodies but did not recognize the entire protein Ro60 (TROVE2), a behaviour similar to that of sera from patients with Cogan syndrome. In conclusion the data obtained so far show that anti-inner ear antibodies do not recognize the entire protein TROVE2 and do not support the hypothesis that such antibodies may be involved in the pathogenesis of congenital heart block. © 2017 SAGE Publications.


Morciano G.,University of Ferrara | Sarti A.C.,University of Ferrara | Marchi S.,University of Ferrara | Missiroli S.,University of Ferrara | And 6 more authors.
Nature protocols | Year: 2017

ATP, the energy exchange factor that connects anabolism and catabolism, is required for major reactions and processes that occur in living cells, such as muscle contraction, phosphorylation and active transport. ATP is also the key molecule in extracellular purinergic signaling mechanisms, with an established crucial role in inflammation and several additional disease conditions. Here, we describe detailed protocols to measure the ATP concentration in isolated living cells and animals using luminescence techniques based on targeted luciferase probes. In the presence of magnesium, oxygen and ATP, the protein luciferase catalyzes oxidation of the substrate luciferin, which is associated with light emission. Recombinantly expressed wild-type luciferase is exclusively cytosolic; however, adding specific targeting sequences can modify its cellular localization. Using this strategy, we have constructed luciferase chimeras targeted to the mitochondrial matrix and the outer surface of the plasma membrane. Here, we describe optimized protocols for monitoring ATP concentrations in the cytosol, mitochondrial matrix and pericellular space in living cells via an overall procedure that requires an average of 3 d. In addition, we present a detailed protocol for the in vivo detection of extracellular ATP in mice using luciferase-transfected reporter cells. This latter procedure may require up to 25 d to complete.


Rosado M.M.,Immunology Area | Nasta F.,ENEA | Prisco M.G.,ENEA | Prisco M.G.,Catholic University of the Sacred Heart | And 3 more authors.
Bioelectromagnetics | Year: 2014

Studies describing the influence of radiofrequency electromagnetic fields on bone marrow cells (BMC) often lack functional data. We examined the effects of in vivo exposure to a Global System for Mobile Communications (GSM) modulated 900MHz RF fields on BMC using two transplantation models. X-irradiated syngeneic mice were injected with BMC from either RF-field-exposed, sham-exposed or cage control mice. Twelve weeks after transplantation, no differences in thymocyte number, frequency of subpopulations and cell proliferation were found in mice receiving BMC from either group. Also, in the spleen cell number, percentages of B/T cells, B/T-cell proliferation, and interferon γ (IFN-γ) production were similar in all groups. In parallel, a mixture of BMC from congenic sham- and RF-exposed mice were co-transplanted into lymphopenic Rag2 deficient mice. BMC from RF-exposed and sham-exposed mice displayed no advantage or disadvantage when competing for the replenishment of lymphatic organs with mature lymphocytes in Rag2 deficient mice. This model revealed that BMC from sham-exposed and RF-exposed mice were less efficient than BMC from cage control mice in repopulating the thymus, an effect likely due to restraint stress. In conclusion, our results showed no effects of in vivo exposure to GSM-modulated RF-fields on the ability of bone marrow (BM) precursors to long-term reconstitute peripheral T and B cell compartments. © 2014 Wiley Periodicals, Inc.


PubMed | Immunology Area
Type: Journal Article | Journal: Bioelectromagnetics | Year: 2014

Studies describing the influence of radiofrequency electromagnetic fields on bone marrow cells (BMC) often lack functional data. We examined the effects of in vivo exposure to a Global System for Mobile Communications (GSM) modulated 900 MHz RF fields on BMC using two transplantation models. X-irradiated syngeneic mice were injected with BMC from either RF-field-exposed, sham-exposed or cage control mice. Twelve weeks after transplantation, no differences in thymocyte number, frequency of subpopulations and cell proliferation were found in mice receiving BMC from either group. Also, in the spleen cell number, percentages of B/T cells, B/T-cell proliferation, and interferon (IFN-) production were similar in all groups. In parallel, a mixture of BMC from congenic sham- and RF-exposed mice were co-transplanted into lymphopenic Rag2 deficient mice. BMC from RF-exposed and sham-exposed mice displayed no advantage or disadvantage when competing for the replenishment of lymphatic organs with mature lymphocytes in Rag2 deficient mice. This model revealed that BMC from sham-exposed and RF-exposed mice were less efficient than BMC from cage control mice in repopulating the thymus, an effect likely due to restraint stress. In conclusion, our results showed no effects of in vivo exposure to GSM-modulated RF-fields on the ability of bone marrow (BM) precursors to long-term reconstitute peripheral T and B cell compartments.

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