Umberto Dianzani

Amedeo Avogadro University of Eastern Piedmont, Novara, Piedmont, Italy

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Publications (165)768.04 Total impact

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    ABSTRACT: Perforin (PRF) has a key role in the function of cytotoxic T and natural killer cells. Rare variations of PRF1 predispose to autoimmunity. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, involving defective lymphocyte apoptosis. The aim of this study was to investigate the role of PRF1 in CIDP. The entire coding region of PRF1 was sequenced in 94 patients and 158 controls. We found three missense variations leading to amino acid substitutions and one nonsense variation resulting in a premature stop codon. All variations would decrease PRF activity. Their overall frequency was significantly higher in patients than in controls (odds ratio (OR)=4.47). The most frequent variation was p.Ala91Val (OR=3.92) previously associated with other autoimmune diseases. Clinical analysis showed that PRF1 variations were more frequent in relapsing patients and in patients displaying axonal damage. These data suggest that PRF1 variations may influence CIDP development and course.Genes and Immunity advance online publication, 30 October 2014; doi:10.1038/gene.2014.59.
    Genes and immunity. 10/2014;
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    ABSTRACT: Circulating levels of soluble urokinase-like plasminogen activator receptor (suPAR) have been associated with proteinuria and renal function in focal segmental glomerulosclerosis (FSGS). This study aimed to evaluate if circulating suPAR levels are independently associated with proteinuria in patients with non-FSGS glomerulonephritis.
    Journal of nephrology. 09/2014;
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    ABSTRACT: "Inverse vaccination" refers to antigen-specific tolerogenic immunization treatments that are capable of inhibiting autoimmune responses. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), initial trials using purified myelin antigens required repeated injections because of the rapid clearance of the antigens. This problem has been overcome by DNA-based vaccines encoding for myelin autoantigens alone or in combination with "adjuvant" molecules, such as interleukin (IL)-4 or IL-10, that support regulatory immune responses. Phase I and II clinical trials with myelin basic protein (MBP)-based DNA vaccines showed positive results in reducing magnetic resonance imaging (MRI)-measured lesions and inducing tolerance to myelin antigens in subsets of MS patients. However, DNA vaccination has potential risks that limit its use in humans. An alternative approach could be the use of protein-based inverse vaccines loaded in polymeric biodegradable lactic-glycolic acid (PLGA) nano/microparticles (NP) to obtain the sustained release of antigens and regulatory adjuvants. The aim of this work was to test the effectiveness of PLGA-NP loaded with the myelin oligodendrocyte glycoprotein (MOG)35-55 autoantigen and recombinant (r) IL-10 to inverse vaccinate mice with EAE. In vitro experiments showed that upon encapsulation in PLGA-NP, both MOG35-55 and rIL-10 were released for several weeks into the supernatant. PLGA-NP did not display cytotoxic or proinflammatory activity and were partially endocytosed by phagocytes. In vivo experiments showed that subcutaneous prophylactic and therapeutic inverse vaccination with PLGA-NP loaded with MOG35-55 and rIL-10 significantly ameliorated the course of EAE induced with MOG35-55 in C57BL/6 mice. Moreover, they decreased the histopathologic lesions in the central nervous tissue and the secretion of IL-17 and interferon (IFN)-γ induced by MOG35-55 in splenic T cells in vitro. These data suggest that subcutaneous PLGA-NP-based inverse vaccination may be an effective tool to treat autoimmune diseases.
    Vaccine. 08/2014;
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    ABSTRACT: Osteopontin (OPN) and soluble urokinase plasminogen activator receptor (suPAR) have been proposed as markers of disease severity and risk--stratification in infection and inflammation. In breast cancer, OPN and the membrane bound form of urokinase plasminogen activator receptor (uPAR) are functionally related, as OPN--induced cell migration depends on uPAR triggering by urokinase plasminogen activator (uPA). The aim of this study was to prospectively evaluate the kinetic of OPN and super blood levels in patients developing septic shock (SS) compared to those not developing SS, and to investigate the relationships between these two biomarkers in immune cells in vitro.
    Minerva anestesiologica 07/2014; · 2.82 Impact Factor
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    ABSTRACT: Elevated serum levels of osteopontin have been associated with cardiovascular disease, diabetic nephropathy, and autoimmune disease activity. Aim of the study was to investigate the relationship between osteopontin serum levels and renal damage in a population of patients with systemic lupus erythematosus (SLE). Osteopontin serum levels were analyzed in 101 SLE patients and compared to those of 115 healthy controls. Associations between osteopontin levels and renal involvement, disease activity and damage index, biochemical parameters, and therapy were assessed. Overall osteopontin serum levels were higher in SLE patients (median, 17.93 ng/mL; interquartile range, 8.13-35.07 ng/mL) than in healthy controls (median, 5.62 ng/mL; interquartile range, 2.61-13.83 ng/mL). Univariate logistic analysis among cases showed that high osteopontin levels (higher vs medium-lower tertile) were associated with renal involvement (p = 0.012), renal function (p = 0.007), proteinuria (p = 0.011), anemia (p < 0.001), and SLICC/ACR Damage Index (p < 0.001). Multivariate analysis showed an independent association between high osteopontin serum levels (higher vs medium-lower tertile) and chronic kidney disease (OR = 4.89; 95 % CI, 1.24-19.24; p = 0.008), proteinuria (OR = 4.56; 95 % CI, 1.15-18.04; p = 0.027), anemia (OR = 4.66; 95 % CI, 1.25-17.43; p = 0.008), and use of renin-angiontensin system antagonists (OR = 0.234; 95 % CI, 0.06-0.98; p = 0.047). This study shows that elevated osteopontin serum levels significantly correlate with renal involvement and anemia in SLE. Moreover, it suggests that renin-angiontensin system antagonists decrease osteopontin levels-this effect is consistent with the inhibitory effect of these drugs on osteopontin renal expression, detected in animal models by other authors, and may provide a new rationale for their employment.
    Clinical Rheumatology 05/2014; · 2.04 Impact Factor
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    ABSTRACT: Vascular endothelial cells (ECs) and several cancer cells express B7h, which is the ligand of the ICOS T cell costimulatory molecule. We have previously shown that B7h triggering via a soluble form of ICOS (ICOS-Fc) inhibits the adhesion of polymorphonuclear and tumor cell lines to HUVECs; thus, we suggested that ICOS-Fc may act as an anti-inflammatory and antitumor agent. Because cancer cell migration and angiogenesis are crucial for metastasis dissemination, the aim of this work was to evaluate the effect of ICOS-Fc on the migration of cancer cells and ECs. ICOS-Fc specifically inhibited the migration of HUVECs, human dermal lymphatic ECs, and the HT29, HCT116, PC-3, HepG2, JR8, and M14 tumor cell lines expressing high levels of B7h, whereas it was ineffective in the RPMI7932, PCF-2, LM, and BHT-101 cell lines expressing low levels of B7h. Furthermore, ICOS-Fc downmodulated hepatocyte growth factor facilitated the epithelial-to-mesenchymal transition in HepG2 cells. Moreover, ICOS-Fc downmodulated the phosphorylation of focal adhesion kinase and the expression of β-Pix in both HUVECs and tumor cell lines. Finally, treatment with ICOS-Fc inhibited the development of lung metastases upon injection of NOD-SCID-IL2Rγnull mice with CF-PAC1 cells, as well as C57BL/6 mice with B16-F10 cells. Therefore, the B7h-ICOS interaction may modulate the spread of cancer metastases, which suggests the novel use of ICOS-Fc as an immunomodulatory drug. However, in the B16-F10-metastasized lungs, ICOS-Fc also increased IL-17A/RORc and decreased IL-10/Foxp3 expression, which indicates that it also exerts positive effects on the antitumor immune response.
    The Journal of Immunology 04/2014; · 5.52 Impact Factor
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    ABSTRACT: Inducible Co-stimulator (ICOS) plays a critical role in mediating T cell differentiation and function and is considered a key player in balancing T effector and T regulatory (Treg) cell responses. Here we show that activation of the ICOS signalling pathway during acute influenza A virus (IAV) infection by application of an agonistic ICOS antibody reduced the frequency of CD8+ T cells in the respiratory tract of IAV infected animals and delayed pathogen elimination. In line with this, immune-mediated influenza pneumonia was significantly ameliorated in mice that received ICOS agonist as indicated by significantly reduced alveolar infiltrations and bronchointerstitial pneumonia, while at the same time virus-related pathology remained unaffected. Importantly, ICOS agonist treatment resulted in expansion of CD4+Foxp3+ Tregs in IAV infected mice, which was associated with elevated levels of the immunosuppressive cytokine IL-10 in the alveolar space. Together, our findings suggest a prominent role of ICOS signaling during acute IAV infection by increasing the Treg/CD8+ T cell ratio with beneficial outcome on immune-mediated pneumonia and underline the suitability of ICOS as potential therapeutic target for immune intervention in those infectious conditions characterized by strong immunopathology rather than virus-mediated cytopathic effects.
    PLoS ONE 01/2014; 9(7):e100970. · 3.53 Impact Factor
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    Autoimmune diseases. 01/2014; 2014:812847.
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    ABSTRACT: In autoimmune/lymphoproliferative syndrome (ALPS), defective Fas death receptor function causes lymphadenomegaly/splenomegaly, the expansion of TCRαβ(+) CD4/CD8 double-negative (DN) T cells, and frequent development of hematologic autoimmunity. Dianzani Autoimmune Lymphoproliferative Disease (DALD) has a similar phenotype but lacks the expansion of DN T cells. This work shows that patients with ALPS and DALD have high serum levels of IL-17A, IL-17F and IL-17AF, which are involved in several autoimmune diseases, and that their T cells show increased secretion of these cytokines upon activation in vitro. The following data indicate that these cytokines may contribute to ALPS and DALD: 1) recombinant IL-17A and IL-17F significantly inhibit Fas-induced cell death (FICD) in Fas-sensitive T cells from healthy donors; 2) this inhibitory effect is also induced by the patients' serum and is reversed by anti-IL-17A antibodies; 3) IL-17A neutralization substantially increases FICD in T cells from ALPS and DALD patients in vitro and 4) treatment with anti-IL-17A antibodies ameliorates the autoimmune manifestations and, at a lesser extent, the lymphoproliferative phenotype and prolongs survival in MRLlpr/lpr mice, which are an animal model of ALPS. These data suggest that IL-17A and IL-17F could be targeted therapeutically to improve Fas function in ALPS and DALD.
    Blood 12/2013; · 9.78 Impact Factor
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    ABSTRACT: This article presents a case report for a child presenting with mixed clinical features of autoimmune lymphoproliferative syndrome (ALPS), familial hemophagocytic lymphohistiocytosis (FHL), and X-linked lymphoproliferative (XLP) disease. From 6 months, he exhibited splenomegaly and lymphoadenopathy and from 4 years, he showed recurrent severe autoimmune hemocytopenia and sepsislike bouts of fever, from which he eventually died at the age of 12. Intriguingly, the patient carried mutations in FAS, XIAP, and UNC13D genes, which are involved in ALPS, XLP disease, and FHL, respectively. These mutations were inherited from the mother, who had rheumatoid arthritis but no signs of ALPS. A role for other modifying genes was suggested by the finding that the healthy father exhibited defective Fas function, without mutation of the FAS gene, and had transmitted to the patient an osteopontin (OPN) gene variant previously associated with ALPS. Therefore, several genes might influence the disease outcome in this family. In vitro analyses revealed that the FAS and the XIAP mutations decreased expression of the corresponding proteins, and the UNC13D mutation decreased granule secretion and Munc interaction with Rab-27a. These findings suggest that overlap may exist between ALPS, FHL, and XLP disease, in accordance with the notion that FHL and XLP disease are due to defective natural killer (NK)/NK T-cell function, which involves Fas. Therefore, we propose that NK cell defects should be evaluated in patients with ALPS-like characteristics, and hematopoietic stem cell transplantation should be considered in individuals with severe refractory cytopenia and FHL-like manifestations.
    PEDIATRICS 09/2013; · 4.47 Impact Factor
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    ABSTRACT: ICOS and CD28 are expressed by T cells and are involved in costimulation of cytokine production in T helper (TH) cells. ICOS binds B7h expressed by several cell types, whereas CD28 binds B7.1 and B7.2 expressed by activated antigen presenting cells. This work investigated the role of B7h and B7.1 in TH17 and TH9 cell differentiation by assessing activity of recombinant B7h-Fc and B7.1-Fc on human naïve TH cells activated in the presence of different combinations of exogenous cytokines. In the presence of TGF-β1 and IL-1β (TH17 promoting condition), B7h-Fc was more effective than B7.1-Fc in inducing IL-17A and IL-10 secretion, whereas B7.1-Fc was more effective in inducing IL-17F. Dual costimulation with B7h-Fc and B7.1-Fc displayed an intermediate pattern with predominance of IL-17F over IL-17A, secretion of high levels of IL-10, and secretion of IL-9 levels lower than those induced by B7.1-Fc alone. In the presence of TGF-β1 and IL-4 (TH9 promoting condition), B7h-Fc induced IL-17A only, whereas B7.1-Fc induced also IL-17F, IL-10, and high levels of IL-9. Experiments on memory TH cells showed that B7h-Fc mainly supported secretion of IL-17A and IL-10, whereas B7.1-Fc supported secretion of IL-17A, IL-17F, IL-10, and IL-9. These data indicate that B7h and B7.1 play different roles in modulation of TH17 and TH9 differentiation. This plasticity might be important in the immune response to pathogens and tumors, and in the development of autoimmune diseases, and should be taken in consideration in designing of immunotherapeutic protocols triggering ICOS or CD28.
    Cytokine 06/2013; · 2.52 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Cholesteryl butyrate solid lipid nanoparticles (cholbut SLN) can be a delivery system for the anti-cancer drug butyrate. We have previously shown that they inhibit adhesion of polymorphonuclear and tumor cells to endothelial cells and migration of tumor cells, suggesting that they may act as anti-inflammatory and antitumor agents. The aim of the research was to evaluate the activity of cholbut SLN on tumor cell growth using in vitro and in vivo models. EXPERIMENTAL APPROACH: Cholbut SLN were incubated with four tumor cell lines, and cell growth was analysed by assessing viability, clonogenic capacity and cell cycle. The effect on signalling was evaluated by western blot analysis of Akt expression. The in vivo anti-tumor activity was assessed using two models of PC-3 cell xenografts in SCID/beige mice. KEY RESULTS: Cholbut SLN inhibited tumor cell line viability, clonogenic activity, Akt phosphorylation, and cell cycle progression. Mice were injected i.v. with PC3-Luc cells and treated with cholbut SLN. In vivo optical imaging and histological analysis showed that no metastases were detected in the lungs of the treated mice. Mice were injected s.c. with PC-3 cells and treated with cholbut SLN when the tumor diameter reached 2 mm. Analysis of the tumor dimensions showed that treatment with cholbut SLN substantially delayed tumor growth. CONCLUSION AND IMPLICATIONS: These results demonstrated that cholbut SLN is effective in inhibiting tumor growth and suggest that this effect may partly involve inhibition of AKT phosphorylation, which adds another mechanism to the activity of this multifaceted drug.
    British Journal of Pharmacology 05/2013; · 5.07 Impact Factor
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    ABSTRACT: Immune reactions inside the central nervous system are finely regulated, thanks to the presence of several checkpoints that have the fundamental purpose to preserve this fragile tissue form harmful events. The current knowledge on the role of neuroinflammation and neuro-immune interactions in the fields of multiple sclerosis, Alzheimer's disease and Parkinson's disease is reviewed. Moreover, a focus on the potential role of both active and passive immunotherapy is provided. Finally, we propose a common perspective, which implies that, under pathological conditions, inflammation may exert both detrimental and protective functions, depending on local factors and the timing of immune activation and shutting-off systems.
    American journal of neurodegenerative disease. 01/2013; 2(2):89-107.
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    ABSTRACT: Autoimmune lymphoproliferative syndrome (ALPS) is caused by genetic defects decreasing Fas function and is characterized by lymphadenopathy/splenomegaly and expansion of CD4/CD8 double-negative T cells. This latter expansion is absent in the ALPS variant named Dianzani Autoimmune/lymphoproliferative Disease (DALD). In addition to the causative mutations, the genetic background influences ALPS and DALD development. We previously suggested a disease-modifying role for the perforin gene involved in familial hemophagocytic lymphohistiocytosis (FHL). The UNC13D gene codes for Munc13-4, which is involved in perforin secretion and FHL development, and thus, another candidate for a disease-modifying role in ALPS and DALD. In this work, we sequenced UNC13D in 21 ALPS and 20 DALD patients and compared these results with sequences obtained from 61 healthy subjects and 38 multiple sclerosis (MS) patients. We detected four rare missense variations in three heterozygous ALPS patients carrying p.Cys112Ser, p.Val781Ile, and a haplotype comprising both p.Ile848Leu and p.Ala995Pro. Transfection of the mutant cDNAs into HMC-1 cells showed that they decreased granule exocytosis, compared to the wild-type construct. An additional rare missense variation, p.Pro271Ser, was detected in a healthy subject, but this variation did not decrease Munc13-4 function. These data suggest that rare loss-of-function variations of UND13D are risk factors for ALPS development.
    PLoS ONE 01/2013; 8(7):e68045. · 3.53 Impact Factor
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    ABSTRACT: B7h, expressed by several cell types, binds ICOS expressed by activated T cells. We have previously shown that B7h triggering by ICOS-Fc inhibits human endothelial cell adhesiveness. This work investigated the effect of ICOS-Fc on human monocyte-derived dendritic cells (DCs). We found that DCs matured with LPS in the presence of ICOS-Fc (mDCs(ICOS)) produced greater amounts of IL-23 and IL-10, and promoted a higher secretion of IL-17A and IL-17F in MLCs than did those DCs matured with LPS alone (mDCs). Moreover, mDCs(ICOS) pulsed with the keyhole limpet hemocyanin Ag during the maturation phase were better stimulators of Ag-specific MHC class I-, but not class II-restricted T cells than mDCs. This was probably due to promotion of cross-presentation because it was not detected when the Flu-MA(58-66) Ag was directly loaded on already matured DCs and mDCs(ICOS). Finally, ICOS-Fc inhibited the adhesion of both immature DCs and mDCs to vascular and lymphoid endothelial cells, their migratory activity, and the expression of the Rac-1 activator β-Pix involved in cell motility. These data suggest that B7h stimulation modulates DC function with effects on their maturation and recruitment into tissues. This opens a novel view on the use of interactors of the ICOS:B7h system as immunomodulatory drugs.
    The Journal of Immunology 12/2012; · 5.52 Impact Factor
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    ABSTRACT: Clustering of Autoimmune Diseases (CAD) is now emerging as a novel clinical entity within monogenic immune defects with a high familial occurrence. Aim of this study is to evaluate the regulatory mechanisms governing cell survival, paying a particular attention to Fas-induced apoptosis, in a cohort of 23 children affected with CAD. In 14 patients, Fas stimulation failed to induce cell apoptosis and in 1 case it was associated with Fas gene mutation. Our study highlights the importance to evaluate cell apoptosis in the group of children with CAD, which, with this regard, represents a distinct clinical entity.
    Italian Journal of Pediatrics 09/2012; 38:42. · 1.34 Impact Factor
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    ABSTRACT: BACKGROUND: The endocannabinoid system reportedly plays a role in the pathogenesis of cardiovascular diseases. This system is expressed also in adipose tissue, which could thus be involved in cardiac disorders through modulation of metabolically triggered inflammation. The current study aims to determine the relevance of the endocannabinoid system in epicardial adipose tissue in heart disease. METHODS: Expression of the endocannabinoid receptors CB1 and CB2, and of the endocannabinoid-degrading enzyme, fatty acid amidohydrolase, and activation of protein kinase A (PKA), phospholipase C (PLC), protein kinase C (PKC), endothelial nitric oxide synthase (eNOS) and inducible (i)NOS, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (a member of the reperfusion-injury salvage kinase pathway), were analyzed by Western blot in patients after coronary artery bypass surgery (ischemics; N = 18) or valve surgery (nonischemics; N = 15) and in preadipocytes isolated from epicardial adipose tissue. RESULTS: In ischemics, the CB1-to-CB2 expression ratio shifted toward CB1 and was accompanied by higher PKA activation. In contrast, in nonischemics, CB2, fatty acid amidohydrolase, PLC and PKC, and ERK1/2 were upregulated. Moreover, NO production and iNOS-to-eNOS ratios were higher in preadipocytes from ischemics. CONCLUSIONS: These results show a different modulation and functioning of the endocannabinoid system in ischemics compared with nonischemics. Hence, while CB2, PLC and PKC, ERK1/2, and eNOS are more strongly expressed in patients without ischemic heart disease, high CB1 and PKA expression is associated with low survival intracellular pathway activation and high iNOS activation in ischemic heart disease patients. The changes in the endocannabinoid system in ischemics may contribute to cardiac dysfunction and therefore represents a potential therapeutic target.
    The Canadian journal of cardiology 08/2012; · 3.12 Impact Factor
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    C Comi, T Fleetwood, U Dianzani
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    ABSTRACT: Fas is a transmembrane receptor involved in the death program of several cell lines, including T lymphocytes. Deleterious mutations hitting genes involved in the Fas pathway cause the autoimmune lymphoprolipherative syndrome (ALPS). Moreover, defective Fas function is involved in the development of common autoimmune diseases, including autoimmune syndromes hitting the nervous system, such as multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). In this review, we first explore some peculiar aspects of Fas mediated apoptosis in the central versus peripheral nervous system (CNS, PNS); thereafter, we analyze what is currently known on the role of T cell apoptosis in both MS and CIDP, which, in this regard, may be seen as two faces of the same coin. In fact, we show that, in both diseases, defective Fas mediated apoptosis plays a crucial role favoring disease development and its chronic evolution.
    Autoimmunity reviews 04/2012; · 6.37 Impact Factor
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    ABSTRACT: In hepatitis C virus (HCV)-associated liver disease, the immune system is unable to clear the viral infection. Previous studies have raised the possibility of an involvement of regulatory T cells (Tregs). In this study, we analysed the peripheral blood from 30 patients with HCV-associated chronic liver disease and 20 healthy controls by flow cytometry for the evaluation of the Treg population [CD4⁺CD25hi forkhead box protein 3 (Foxp3)⁺], as well as the activated/effector CD4⁺ T cells (CD4⁺CD25low) and IFN-γ-secreting cells. We also analysed liver biopsies of the patients by immunohistochemical evaluation of Foxp3⁺ cells. Our results showed higher proportions of CD4⁺CD25low and IFN-γ⁺ cells in the patients than in the controls. By contrast, the proportions of peripheral CD4⁺CD25hi cells did not significantly differ. The 11 patients displaying Foxp3⁺ cells in the liver infiltrates showed significantly higher proportions of peripheral CD4⁺CD25low cells. Moreover, we found lower serum transaminase levels in the patients than in the controls, as shown by Foxp3⁺ immunohistochemistry, although these results were only statistically significant as regards alanine transaminase (ALT). In conclusion, these data suggest that the presence of Tregs infiltrating the liver is associated with high levels of activated/effector T cells in the peripheral blood and lower activity of hepatitis. Therefore, liver-infiltrating Tregs may play a role in limiting tissue damage and may thus support an effective immune response against HCV.
    International Journal of Molecular Medicine 03/2012; 29(6):983-8. · 1.96 Impact Factor
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    ABSTRACT: Inherited defects decreasing function of the Fas death receptor cause autoimmune lymphoproliferative syndrome (ALPS) and its variant Dianzani autoimmune lymphoproliferative disease (DALD). Since a deleterious mutation of the SH2D1A gene protects MRLlpr/lpr mice from ALPS development, we investigated the role of SH2D1A, located in the X chromosome, in 51 patients with ALPS or DALD by mutational screening of coding and regulative sequences. Allelic frequency of the -346C>T polymorphism was different in male patients and controls (-346T: 61% vs 36%, p = 0.01), with similar frequencies in ALPS and DALD. By contrast, no differences were found among females or between the controls and patients with multiple sclerosis (229 males, 157 females). Further analyses showed that -346C was a methylation site in CD8(+) T and natural killer cells, and SH2D1A expression was higher in -346T than in -346C males. Finally, in vitro-activated T cells from -346T males produced lower amounts of interferon-γ than those from -346C males. These data suggest that -346T is a predisposing factor for ALPS and DALD in males possibly because of its effect on SAP expression influencing the T-cell response.
    Human immunology 03/2012; 73(5):585-92. · 2.55 Impact Factor

Publication Stats

3k Citations
768.04 Total Impact Points

Institutions

  • 1999–2014
    • Amedeo Avogadro University of Eastern Piedmont
      • Interdisciplinary Research Center of Autoimmune Diseases IRCAD
      Novara, Piedmont, Italy
  • 2013
    • Ospedale Pediatrico Meyer Firenze
      Florens, Tuscany, Italy
  • 1983–2013
    • Università degli Studi di Torino
      • • Dipartimento di Scienze Mediche
      • • Dipartimento di Scienza e Tecnologia del Farmaco
      • • Dipartimento di Scienze Cliniche e Biologiche
      • • Dipartimento di Scienze Chirurgiche
      Torino, Piedmont, Italy
  • 2003–2010
    • Spanish National Research Council
      • Biological Research Centre
      Madrid, Madrid, Spain
  • 2002–2008
    • Tokyo Women's Medical University
      • • Department of Oral and Maxillofacial Surgery
      • • Department of Microbiology and Immunology
      Edo, Tōkyō, Japan
  • 2006
    • University of Pavia
      Ticinum, Lombardy, Italy
  • 2000
    • University of Naples Federico II
      Napoli, Campania, Italy
  • 1990–1994
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • Yale University
      • Department of Immunobiology
      New Haven, CT, United States
  • 1993
    • Polo d'Innovazione di Genomica Genetica e Biologia
      Perugia, Umbria, Italy
    • Università di Pisa
      Pisa, Tuscany, Italy