Francesco Ria - Profile on Academia.edu (original) (raw)
Papers by Francesco Ria
Liposome-based nanoparticles impact on regulatory and effector phenotypes of macrophages and T cells in multiple Sclerosis patients
Biomaterials
Molecular Neurobiology
Several biomarkers from multiple sclerosis (MS) patients’ biological fluids have been considered ... more Several biomarkers from multiple sclerosis (MS) patients’ biological fluids have been considered to support diagnosis, predict disease course, and evaluate treatment response. In this study, we assessed the CSF concentration of selected molecules implicated in the MS pathological process. To investigate the diagnostic and prognostic significance of CSF concentration of target candidate biomarkers in both relapsing (RMS, n = 107) and progressive (PMS, n = 18) MS patients and in other inflammatory (OIND, n = 10) and non-inflammatory (ONIND, n = 15) neurological disorders. We measured the CSF concentration of APRIL, BAFF, CHI3L1, CCL-2, CXCL-8, CXCL-10, CXCL-12, CXCL-13 through a Luminex Assay. MS patients were prospectively evaluated, and clinical and radiological activity were recorded. CHI3L1 and CXCL13 CSF levels were significantly higher in both MS groups compared to control groups, while CCL2, BAFF, and APRIL concentrations were lower in RMS patients compared to PMS and OIND. Con...
iScience, 2022
Highlights Environment and genetic are both involved in the regulation of T cell motility Pathoge... more Highlights Environment and genetic are both involved in the regulation of T cell motility Pathogens and commensals impact on T cell trafficking through a TLRs/CD44v axis Regulation of CD44 isoforms by TLRs is a new pathogenetic mechanism of autoimmunity Modulation of CD44 isoform can be a new target for therapy of multiple sclerosis
Critical Reviews in Immunology, 2020
The contribution of Eli E. Sercarz to immunology and immunopathology has been remarkable and achi... more The contribution of Eli E. Sercarz to immunology and immunopathology has been remarkable and achieved many milestones in the understanding of the processes of the mechanisms fine-tuning immune responses. A part of his work was dedicated to the study of the deep complexity of the lymphocyte T cell repertoire and its importance during the physiologic development and disease, such as clonal heterogeneity of T cell responses. Starting from these studies, under his mentoring, we had the opportunity to implement the spectratyping method and apply it to human and experimental autoimmune diseases, obtaining intriguing results. The open question of this brief review is the possible role of this fine and complex technique, the immunoscope analysis, in the era of the big data and omics.
Children
While the clinical impact of COVID-19 on adults has been massive, the majority of children develo... more While the clinical impact of COVID-19 on adults has been massive, the majority of children develop pauci-symptomatic or even asymptomatic infection and only a minority of the latter develop a fatal outcome. The reasons of such differences are not yet established. We examined cytokines in sera and Th and B cell subpopulations in peripheral blood mononuclear cells (PBMC) from 40 children (<18 years old), evaluating the impact of COVID-19 infection during the pandemic’s first waves. We correlated our results with clinical symptoms and compared them to samples obtained from 16 infected adults and 7 healthy controls. While IL6 levels were lower in SARS-CoV-2+ children as compared to adult patients, the expression of other pro-inflammatory cytokines such as IFNγ and TNFα directly correlated with early age infection and symptoms. Th and B cell subsets were modified during pediatric infection differently with respect to adult patients and controls and within the pediatric group based on ...
Fighting autoinflammation in FIRES: the role of interleukins and early immunomodulation
Epilepsy & Behavior Reports, 2022
Growing role of S100B protein as a putative therapeutic target for neurological- and nonneurological-disorders
Neuroscience & Biobehavioral Reviews, 2021
S100B is a calcium-binding protein mainly expressed by astrocytes, but also localized in other de... more S100B is a calcium-binding protein mainly expressed by astrocytes, but also localized in other definite neural and extra-neural cell types. While its presence in biological fluids is widely recognized as a reliable biomarker of active injury, growing evidence now indicates that high levels of S100B are suggestive of pathogenic processes in different neural, but also extra-neural, disorders. Indeed, modulation of S100B levels correlates with the occurrence of clinical and/or toxic parameters in experimental models of diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, muscular dystrophy, multiple sclerosis, acute neural injury, inflammatory bowel disease, uveal and retinal disorders, obesity, diabetes and cancer, thus directly linking the levels of S100B to pathogenic mechanisms. In general, deletion/inactivation of the protein causes the improvement of the disease, whereas its over-expression/administration induces a worse clinical presentation. This scenario reasonably proposes S100B as a common therapeutic target for several different disorders, also offering new clues to individuate possible unexpected connections among these diseases.
Increased levels of Manganese-Superoxidedismutase in brain neuroepithelial tumors: correlation with degree of anaplasia
Allergy, 2019
Association between asthma ad hypersensitivity to specific molecules in patients monosensitized t... more Association between asthma ad hypersensitivity to specific molecules in patients monosensitized to house dust mites. A clear association with Der p 23 hypersensitivity is observed. Left column: asthmatic patients; right column: nonasthmatic patients | 3 LETTER TO THE EDITOR
Modulatory Preimplantation Factor Regulates Post-Infectious Experimental Autoimmune Encephalomyelitis in Therapeutic Setting
PreImplantation Factor (PIF, proprietary) regulates inflammatory response in human systemic immun... more PreImplantation Factor (PIF, proprietary) regulates inflammatory response in human systemic immune cells1. Several autoimmune/neuroinflammatory disorders, including Multiple Sclerosis (MS), improve during pregnancy, where PIF may have a protective role. Synthetic PIF (sPIF) replicates native PIF action and regulatory features. sPIF reverses chronic neuroinflammation while promoting neural repair in Experimental Autoimmune Encephalomyelitis (EAE) model2. Herein are examined sPIF modulatory features in our model of post-infectious EAE3. SJL mice were infected with Mycobacterium Smegmatis expressing a recombinant chimeric protein MPT64-PLP139-151 to induce EAE and monitored daily for symptoms. By day 3 after infection, mice were treated by subcutaneous (sc) injections daily (continuously or intermittently at disease peak) with sPIF or vehicle. Lymph node cells from SJL mice were analyzed for levels of pro/anti-inflammatory cytokines, transcription factors (Real Time PCR) and shared T c...
Determination of the Expressed T cell Repertoire: The Outcome of Competition at the Levels of Antigen Presentation and T cell Receptor Recognition
Epitope Recognition Since Landsteiner’s Discovery, 2002
The first half of the 20th century saw a revelation in our understanding of the exquisite specifi... more The first half of the 20th century saw a revelation in our understanding of the exquisite specificity of antibodies, best exemplified in the work by Karl Landsteiner. A single substituent on a hapten could be readily distinguished from a closely related one by an animal’s antiserum. The various antibodies in that antiserum, with their unique perspectives of these cross-reactive haptens/determinants, combined to provide an unmistakable portrait of each region of the antigen. Of course, some antibodies overlapped with others so that, in a sense, a continuum of antibody footprints could be drawn covering the structure.
A Single Non-Synonymous Polymorphism of TLR2 Is responsible for Variability of Experimental Multiple Sclerosis in SJL and B6 Mice
Journal of Immunology Research, 2014
A close relationship exists between gut microbiota and immune responses. An imbalance of this rel... more A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.
Impact of infectious agents on trafficking of effector T cells is mediated by a polymorphic site of TLR2 and CD44 isoforms expression
Frontiers in Immunology, 2013
ABSTRACT
Collagen-specific TCR Repertoire usage in RA and cytokine secretion
Frontiers in Immunology, 2013
ABSTRACT
PPE_MPTR genes are differentially expressed by Mycobacterium tuberculosis in vivo
Tuberculosis, 2011
The PPE_MPTR protein sub-family is unique to mycobacteria and comprises proteins found only in MT... more The PPE_MPTR protein sub-family is unique to mycobacteria and comprises proteins found only in MTB complex and in few other pathogenic mycobacteria. Very little is known about the precise function of PPE_MPTR, as well as on the expression pattern and the transcriptional regulation of their structural genes. In the present work, real time RT-PCR techniques were used to determine the expression profile of PPE_MPTR genes of Mycobacterium tuberculosis during infection in vivo and in different culture conditions. The PPE_MPTR genes showed a similar expression profile in axenic cultures, with a significant increase of gene expression following exposure to environmental signals such as SDS, isoniazid and ethambutol. The PPE_MPTR genes were expressed in lung and spleen tissues infected by M. tuberculosis, and levels of expression were similar to those of genes encoding M. tuberculosis virulence factors such as hbhA and mpt64. Levels and pattern of gene expression in host tissues were different for each PPE_MPTR gene under study. The results of this study indicate that PPE_MPTR genes are differentially regulated in the lung and spleen tissues during M. tuberculosis infection, suggesting that each gene responds independently to the different and complex environmental signals encountered in host tissues.
Journal of the Neurological Sciences, 2011
Environment and genetic are both relevant in determining development of Multiple Sclerosis. Many ... more Environment and genetic are both relevant in determining development of Multiple Sclerosis. Many epidemiological observations converge on indicating EBV infection and Vitamin D levels as major players among the environmental factors. Bacteria and bacterial products are however potent triggers of immune responses, and recent work from several laboratories indicates that the microbiota plays a prominent role in "priming" or protecting individuals for development of experimental autoimmune diseases. Here we report our recent work dealing with the role of non-pathogenic mycobacteria and their innate receptors in relapsing-remitting experimental autoimmune encephalomyelitis in the SJL mouse and in mobilization of CNS-reactive T cells. We finally discuss how bacteria are likely involved in the pathogenesis of Multiple Sclerosis, expecially with regard to their role in driving the recurring acute episodes of disease.
The Journal of Immunology, 2010
Infection and Immunity, 2010
To improve the current vaccine against tuberculosis, a recombinant strain of Mycobacterium bovis ... more To improve the current vaccine against tuberculosis, a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing a Mycobacterium tuberculosis vaccine candidate antigen (MPT64) in strong association with the mycobacterial cell wall was developed. To deliver the candidate antigen on the surface, we fused the mpt64 gene to the sequence encoding the PE domain of the PE_PGRS33 protein of M. tuberculosis (to create strain H PE-ΔMPT64-BCG), which we have previously shown to transport proteins to the bacterial surface. In a series of protection experiments in the mouse model of tuberculosis, we showed that (i) immunization of mice with H PE-ΔMPT64-BCG provides levels of protection significantly higher than those afforded by the parental BCG strain, as assessed by bacterial colonization in lungs and spleens and by lung involvement (at both 28 and 70 days postchallenge), (ii) rBCG strains expressing MPT64 provide better protection than the parental BCG strain only ...
Defective gene expression of MnSOD in tumor cells
Free Radical Biology and Medicine, 1993
Liposome-based nanoparticles impact on regulatory and effector phenotypes of macrophages and T cells in multiple Sclerosis patients
Biomaterials
Molecular Neurobiology
Several biomarkers from multiple sclerosis (MS) patients’ biological fluids have been considered ... more Several biomarkers from multiple sclerosis (MS) patients’ biological fluids have been considered to support diagnosis, predict disease course, and evaluate treatment response. In this study, we assessed the CSF concentration of selected molecules implicated in the MS pathological process. To investigate the diagnostic and prognostic significance of CSF concentration of target candidate biomarkers in both relapsing (RMS, n = 107) and progressive (PMS, n = 18) MS patients and in other inflammatory (OIND, n = 10) and non-inflammatory (ONIND, n = 15) neurological disorders. We measured the CSF concentration of APRIL, BAFF, CHI3L1, CCL-2, CXCL-8, CXCL-10, CXCL-12, CXCL-13 through a Luminex Assay. MS patients were prospectively evaluated, and clinical and radiological activity were recorded. CHI3L1 and CXCL13 CSF levels were significantly higher in both MS groups compared to control groups, while CCL2, BAFF, and APRIL concentrations were lower in RMS patients compared to PMS and OIND. Con...
iScience, 2022
Highlights Environment and genetic are both involved in the regulation of T cell motility Pathoge... more Highlights Environment and genetic are both involved in the regulation of T cell motility Pathogens and commensals impact on T cell trafficking through a TLRs/CD44v axis Regulation of CD44 isoforms by TLRs is a new pathogenetic mechanism of autoimmunity Modulation of CD44 isoform can be a new target for therapy of multiple sclerosis
Critical Reviews in Immunology, 2020
The contribution of Eli E. Sercarz to immunology and immunopathology has been remarkable and achi... more The contribution of Eli E. Sercarz to immunology and immunopathology has been remarkable and achieved many milestones in the understanding of the processes of the mechanisms fine-tuning immune responses. A part of his work was dedicated to the study of the deep complexity of the lymphocyte T cell repertoire and its importance during the physiologic development and disease, such as clonal heterogeneity of T cell responses. Starting from these studies, under his mentoring, we had the opportunity to implement the spectratyping method and apply it to human and experimental autoimmune diseases, obtaining intriguing results. The open question of this brief review is the possible role of this fine and complex technique, the immunoscope analysis, in the era of the big data and omics.
Children
While the clinical impact of COVID-19 on adults has been massive, the majority of children develo... more While the clinical impact of COVID-19 on adults has been massive, the majority of children develop pauci-symptomatic or even asymptomatic infection and only a minority of the latter develop a fatal outcome. The reasons of such differences are not yet established. We examined cytokines in sera and Th and B cell subpopulations in peripheral blood mononuclear cells (PBMC) from 40 children (<18 years old), evaluating the impact of COVID-19 infection during the pandemic’s first waves. We correlated our results with clinical symptoms and compared them to samples obtained from 16 infected adults and 7 healthy controls. While IL6 levels were lower in SARS-CoV-2+ children as compared to adult patients, the expression of other pro-inflammatory cytokines such as IFNγ and TNFα directly correlated with early age infection and symptoms. Th and B cell subsets were modified during pediatric infection differently with respect to adult patients and controls and within the pediatric group based on ...
Fighting autoinflammation in FIRES: the role of interleukins and early immunomodulation
Epilepsy & Behavior Reports, 2022
Growing role of S100B protein as a putative therapeutic target for neurological- and nonneurological-disorders
Neuroscience & Biobehavioral Reviews, 2021
S100B is a calcium-binding protein mainly expressed by astrocytes, but also localized in other de... more S100B is a calcium-binding protein mainly expressed by astrocytes, but also localized in other definite neural and extra-neural cell types. While its presence in biological fluids is widely recognized as a reliable biomarker of active injury, growing evidence now indicates that high levels of S100B are suggestive of pathogenic processes in different neural, but also extra-neural, disorders. Indeed, modulation of S100B levels correlates with the occurrence of clinical and/or toxic parameters in experimental models of diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, muscular dystrophy, multiple sclerosis, acute neural injury, inflammatory bowel disease, uveal and retinal disorders, obesity, diabetes and cancer, thus directly linking the levels of S100B to pathogenic mechanisms. In general, deletion/inactivation of the protein causes the improvement of the disease, whereas its over-expression/administration induces a worse clinical presentation. This scenario reasonably proposes S100B as a common therapeutic target for several different disorders, also offering new clues to individuate possible unexpected connections among these diseases.
Increased levels of Manganese-Superoxidedismutase in brain neuroepithelial tumors: correlation with degree of anaplasia
Allergy, 2019
Association between asthma ad hypersensitivity to specific molecules in patients monosensitized t... more Association between asthma ad hypersensitivity to specific molecules in patients monosensitized to house dust mites. A clear association with Der p 23 hypersensitivity is observed. Left column: asthmatic patients; right column: nonasthmatic patients | 3 LETTER TO THE EDITOR
Modulatory Preimplantation Factor Regulates Post-Infectious Experimental Autoimmune Encephalomyelitis in Therapeutic Setting
PreImplantation Factor (PIF, proprietary) regulates inflammatory response in human systemic immun... more PreImplantation Factor (PIF, proprietary) regulates inflammatory response in human systemic immune cells1. Several autoimmune/neuroinflammatory disorders, including Multiple Sclerosis (MS), improve during pregnancy, where PIF may have a protective role. Synthetic PIF (sPIF) replicates native PIF action and regulatory features. sPIF reverses chronic neuroinflammation while promoting neural repair in Experimental Autoimmune Encephalomyelitis (EAE) model2. Herein are examined sPIF modulatory features in our model of post-infectious EAE3. SJL mice were infected with Mycobacterium Smegmatis expressing a recombinant chimeric protein MPT64-PLP139-151 to induce EAE and monitored daily for symptoms. By day 3 after infection, mice were treated by subcutaneous (sc) injections daily (continuously or intermittently at disease peak) with sPIF or vehicle. Lymph node cells from SJL mice were analyzed for levels of pro/anti-inflammatory cytokines, transcription factors (Real Time PCR) and shared T c...
Determination of the Expressed T cell Repertoire: The Outcome of Competition at the Levels of Antigen Presentation and T cell Receptor Recognition
Epitope Recognition Since Landsteiner’s Discovery, 2002
The first half of the 20th century saw a revelation in our understanding of the exquisite specifi... more The first half of the 20th century saw a revelation in our understanding of the exquisite specificity of antibodies, best exemplified in the work by Karl Landsteiner. A single substituent on a hapten could be readily distinguished from a closely related one by an animal’s antiserum. The various antibodies in that antiserum, with their unique perspectives of these cross-reactive haptens/determinants, combined to provide an unmistakable portrait of each region of the antigen. Of course, some antibodies overlapped with others so that, in a sense, a continuum of antibody footprints could be drawn covering the structure.
A Single Non-Synonymous Polymorphism of TLR2 Is responsible for Variability of Experimental Multiple Sclerosis in SJL and B6 Mice
Journal of Immunology Research, 2014
A close relationship exists between gut microbiota and immune responses. An imbalance of this rel... more A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.
Impact of infectious agents on trafficking of effector T cells is mediated by a polymorphic site of TLR2 and CD44 isoforms expression
Frontiers in Immunology, 2013
ABSTRACT
Collagen-specific TCR Repertoire usage in RA and cytokine secretion
Frontiers in Immunology, 2013
ABSTRACT
PPE_MPTR genes are differentially expressed by Mycobacterium tuberculosis in vivo
Tuberculosis, 2011
The PPE_MPTR protein sub-family is unique to mycobacteria and comprises proteins found only in MT... more The PPE_MPTR protein sub-family is unique to mycobacteria and comprises proteins found only in MTB complex and in few other pathogenic mycobacteria. Very little is known about the precise function of PPE_MPTR, as well as on the expression pattern and the transcriptional regulation of their structural genes. In the present work, real time RT-PCR techniques were used to determine the expression profile of PPE_MPTR genes of Mycobacterium tuberculosis during infection in vivo and in different culture conditions. The PPE_MPTR genes showed a similar expression profile in axenic cultures, with a significant increase of gene expression following exposure to environmental signals such as SDS, isoniazid and ethambutol. The PPE_MPTR genes were expressed in lung and spleen tissues infected by M. tuberculosis, and levels of expression were similar to those of genes encoding M. tuberculosis virulence factors such as hbhA and mpt64. Levels and pattern of gene expression in host tissues were different for each PPE_MPTR gene under study. The results of this study indicate that PPE_MPTR genes are differentially regulated in the lung and spleen tissues during M. tuberculosis infection, suggesting that each gene responds independently to the different and complex environmental signals encountered in host tissues.
Journal of the Neurological Sciences, 2011
Environment and genetic are both relevant in determining development of Multiple Sclerosis. Many ... more Environment and genetic are both relevant in determining development of Multiple Sclerosis. Many epidemiological observations converge on indicating EBV infection and Vitamin D levels as major players among the environmental factors. Bacteria and bacterial products are however potent triggers of immune responses, and recent work from several laboratories indicates that the microbiota plays a prominent role in "priming" or protecting individuals for development of experimental autoimmune diseases. Here we report our recent work dealing with the role of non-pathogenic mycobacteria and their innate receptors in relapsing-remitting experimental autoimmune encephalomyelitis in the SJL mouse and in mobilization of CNS-reactive T cells. We finally discuss how bacteria are likely involved in the pathogenesis of Multiple Sclerosis, expecially with regard to their role in driving the recurring acute episodes of disease.
The Journal of Immunology, 2010
Infection and Immunity, 2010
To improve the current vaccine against tuberculosis, a recombinant strain of Mycobacterium bovis ... more To improve the current vaccine against tuberculosis, a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing a Mycobacterium tuberculosis vaccine candidate antigen (MPT64) in strong association with the mycobacterial cell wall was developed. To deliver the candidate antigen on the surface, we fused the mpt64 gene to the sequence encoding the PE domain of the PE_PGRS33 protein of M. tuberculosis (to create strain H PE-ΔMPT64-BCG), which we have previously shown to transport proteins to the bacterial surface. In a series of protection experiments in the mouse model of tuberculosis, we showed that (i) immunization of mice with H PE-ΔMPT64-BCG provides levels of protection significantly higher than those afforded by the parental BCG strain, as assessed by bacterial colonization in lungs and spleens and by lung involvement (at both 28 and 70 days postchallenge), (ii) rBCG strains expressing MPT64 provide better protection than the parental BCG strain only ...
Defective gene expression of MnSOD in tumor cells
Free Radical Biology and Medicine, 1993