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Article: Immunological Profiles in Parry-Romberg Syndrome: A Case-Control Study.

Saulle, Irma / Gidaro, Antonio / Donadoni, Mattia / Vanetti, Claudia / Mutti, Alessandra / Romano, Maria Eva / Clerici, Mario / Cogliati, Chiara / Biasin, Mara

Journal of clinical medicine

2024 Volume 13, Issue 5

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2024-02-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13051219
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Article ; Online: The role of endoplasmic reticulum aminopeptidases in type 1 diabetes mellitus.

Limanaqi, Fiona / Vicentini, Chiara / Saulle, Irma / Clerici, Mario / Biasin, Mara

Life sciences

2023 Volume 323, Page(s) 121701

Abstract: Type-I diabetes mellitus (T1DM) is generally considered as a chronic, T-cell mediated autoimmune disease. This notwithstanding, both the endogenous characteristics of β-cells, and their response to environmental factors and exogenous inflammatory stimuli ...

Abstract	Type-I diabetes mellitus (T1DM) is generally considered as a chronic, T-cell mediated autoimmune disease. This notwithstanding, both the endogenous characteristics of β-cells, and their response to environmental factors and exogenous inflammatory stimuli are key events in disease progression and exacerbation. As such, T1DM is now recognized as a multifactorial condition, with its onset being influenced by both genetic predisposition and environmental factors, among which, viral infections represent major triggers. In this frame, endoplasmic reticulum aminopeptidase 1 (ERAP1) and 2 (ERAP2) hold center stage. ERAPs represent the main hydrolytic enzymes specialized in trimming of N-terminal antigen peptides to be bound by MHC class I molecules and presented to CD8+ T cells. Thus, abnormalities in ERAPs expression alter the peptide-MHC-I repertoire both quantitatively and qualitatively, fostering both autoimmune and infectious diseases. Although only a few studies succeeded in determining direct associations between ERAPs variants and T1DM susceptibility/outbreak, alterations of ERAPs do impinge on a plethora of biological events which might indeed contribute to the disease development/exacerbation. Beyond abnormal self-antigen peptide trimming, these include preproinsulin processing, nitric oxide (NO) production, ER stress, cytokine responsiveness, and immune cell recruitment/activity. The present review brings together direct and indirect evidence focused on the immunobiological role of ERAPs in T1DM onset and progression, covering both genetic and environmental aspects.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 1/metabolism ; Aminopeptidases/genetics ; Aminopeptidases/metabolism ; Histocompatibility Antigens Class I/metabolism ; Peptides/chemistry ; Endoplasmic Reticulum/metabolism ; Minor Histocompatibility Antigens/metabolism
Chemical Substances	Aminopeptidases (EC 3.4.11.-) ; Histocompatibility Antigens Class I ; Peptides ; Minor Histocompatibility Antigens ; ERAP1 protein, human (EC 3.4.11.-) ; ERAP2 protein, human (EC 3.4.11.-)
Language	English
Publishing date	2023-04-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121701
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Article ; Online: Antigen presentation in SARS-CoV-2 infection: the role of class I HLA and ERAP polymorphisms.

Saulle, Irma / Vicentini, Chiara / Clerici, Mario / Biasin, Mara

Human immunology

2021 Volume 82, Issue 8, Page(s) 551–560

Abstract: Given the highly polymorphic nature of Human Leukocyte Antigen (HLA) molecules, it is not surprising that they function as key regulators of the host immune response to almost all invading pathogens, including SARS-CoV-2, the etiological agent ... ...

Abstract	Given the highly polymorphic nature of Human Leukocyte Antigen (HLA) molecules, it is not surprising that they function as key regulators of the host immune response to almost all invading pathogens, including SARS-CoV-2, the etiological agent responsible for the recent COVID-19 pandemic. Several correlations have already been established between the expression of a specific HLA allele/haplotype and susceptibility/progression of SARS-CoV-2 infection and new ones are continuously emerging. Protective and harmful HLA variants have been described in both mild and severe forms of the disease, but considering the huge amount of existing variants, the data gathered in such a brief span of time are to some extent confusing and contradictory. The aim of this mini-review is to provide a snap-shot of the main findings so far collected on the HLA-SARS-CoV-2 interaction, so as to partially untangle this intricate yarn. As key factors in the generation of antigenic peptides to be presented by HLA molecules, ERAP1 and ERAP2 role in SARS-CoV-2 infection will be revised as well.
MeSH term(s)	Aminopeptidases/genetics ; Aminopeptidases/immunology ; Animals ; Antigen Presentation ; Antigens, Viral/immunology ; COVID-19/diagnosis ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/virology ; Epitopes ; HLA Antigens/genetics ; HLA Antigens/immunology ; Host-Pathogen Interactions ; Humans ; Minor Histocompatibility Antigens/genetics ; Minor Histocompatibility Antigens/immunology ; Polymorphism, Genetic ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity
Chemical Substances	Antigens, Viral ; Epitopes ; HLA Antigens ; Minor Histocompatibility Antigens ; Aminopeptidases (EC 3.4.11.-) ; ERAP1 protein, human (EC 3.4.11.-) ; ERAP2 protein, human (EC 3.4.11.-)
Language	English
Publishing date	2021-05-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2021.05.003
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Article ; Online: Genetic and epigenetic regulation of natural resistance to HIV-1 infection: new approaches to unveil the HESN secret.

Fenizia, Claudio / Saulle, Irma / Clerici, Mario / Biasin, Mara

Expert review of clinical immunology

2020 Volume 16, Issue 4, Page(s) 429–445

Abstract: ... ...

Abstract	Introduction
MeSH term(s)	Animals ; Epigenesis, Genetic ; Genome-Wide Association Study ; HIV Infections/genetics ; HIV Seronegativity/immunology ; HIV-1/physiology ; Humans ; Immunity, Innate ; Proteomics ; Whole Exome Sequencing
Language	English
Publishing date	2020-03-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274260-8
ISSN	1744-8409 ; 1744-666X
ISSN (online)	1744-8409
ISSN	1744-666X
DOI	10.1080/1744666X.2020.1732820
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Article ; Online: An Overview on ERAP Roles in Infectious Diseases.

Saulle, Irma / Vicentini, Chiara / Clerici, Mario / Biasin, Mara

Cells

2020 Volume 9, Issue 3

Abstract: Endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 (ERAPs) are crucial enzymes shaping the major histocompatibility complex I (MHC I) immunopeptidome. In the ER, these enzymes cooperate in trimming the N-terminal residues from precursors peptides, ...

Abstract	Endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 (ERAPs) are crucial enzymes shaping the major histocompatibility complex I (MHC I) immunopeptidome. In the ER, these enzymes cooperate in trimming the N-terminal residues from precursors peptides, so as to generate optimal-length antigens to fit into the MHC class I groove. Alteration or loss of ERAPs function significantly modify the repertoire of antigens presented by MHC I molecules, severely affecting the activation of both NK and CD8
MeSH term(s)	Aminopeptidases/metabolism ; Animals ; Communicable Diseases/genetics ; Humans ; Mice ; Minor Histocompatibility Antigens/metabolism
Chemical Substances	Minor Histocompatibility Antigens ; Aminopeptidases (EC 3.4.11.-) ; ERAP1 protein, mouse (EC 3.4.11.-)
Language	English
Publishing date	2020-03-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9030720
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Article ; Online: The role of endoplasmic reticulum aminopeptidases in type 1 diabetes mellitus

Limanaqi, Fiona / Vicentini, Chiara / Saulle, Irma / Clerici, Mario / Biasin, Mara

Life Sciences. 2023 June, v. 323 p.121701-

2023

Abstract	Type-I diabetes mellitus (T1DM) is generally considered as a chronic, T-cell mediated autoimmune disease. This notwithstanding, both the endogenous characteristics of β-cells, and their response to environmental factors and exogenous inflammatory stimuli are key events in disease progression and exacerbation. As such, T1DM is now recognized as a multifactorial condition, with its onset being influenced by both genetic predisposition and environmental factors, among which, viral infections represent major triggers. In this frame, endoplasmic reticulum aminopeptidase 1 (ERAP1) and 2 (ERAP2) hold center stage. ERAPs represent the main hydrolytic enzymes specialized in trimming of N-terminal antigen peptides to be bound by MHC class I molecules and presented to CD8+ T cells. Thus, abnormalities in ERAPs expression alter the peptide-MHC-I repertoire both quantitatively and qualitatively, fostering both autoimmune and infectious diseases. Although only a few studies succeeded in determining direct associations between ERAPs variants and T1DM susceptibility/outbreak, alterations of ERAPs do impinge on a plethora of biological events which might indeed contribute to the disease development/exacerbation. Beyond abnormal self-antigen peptide trimming, these include preproinsulin processing, nitric oxide (NO) production, ER stress, cytokine responsiveness, and immune cell recruitment/activity. The present review brings together direct and indirect evidence focused on the immunobiological role of ERAPs in T1DM onset and progression, covering both genetic and environmental aspects.
Keywords	T-lymphocytes ; aminopeptidases ; antigens ; autoimmune diseases ; cytokines ; disease progression ; endoplasmic reticulum ; genetic predisposition to disease ; insulin-dependent diabetes mellitus ; nitric oxide ; ERAP1 ; ERAP2 ; MHC-I ; Pancreatic β-cell ; ER stress ; Preproinsulin ; Viral infections
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version ; Use and reproduction
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121701
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells.

Limanaqi, Fiona / Zecchini, Silvia / Saulle, Irma / Strizzi, Sergio / Vanetti, Claudia / Garziano, Micaela / Cappelletti, Gioia / Parolin, Debora / Caccia, Sonia / Trabattoni, Daria / Fenizia, Claudio / Clerici, Mario / Biasin, Mara

Biological research

2024 Volume 57, Issue 1, Page(s) 2

Abstract: Background: Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or ... ...

Abstract	Background: Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. Results: Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-β, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. Conclusions: Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.
MeSH term(s)	alpha-Synuclein ; COVID-19 ; Endothelial Cells ; SARS-CoV-2 ; Humans ; Cell Line ; Interferon Type I ; Virus Replication
Chemical Substances	alpha-Synuclein ; Interferon Type I
Language	English
Publishing date	2024-01-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1138990-4
ISSN	0717-6287 ; 0716-9760
ISSN (online)	0717-6287
ISSN	0716-9760
DOI	10.1186/s40659-023-00482-x
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Article ; Online: An Overview on ERAP Roles in Infectious Diseases

Irma Saulle / Chiara Vicentini / Mario Clerici / Mara Biasin

Cells, Vol 9, Iss 3, p

2020 Volume 720

Abstract	Endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 (ERAPs) are crucial enzymes shaping the major histocompatibility complex I (MHC I) immunopeptidome. In the ER, these enzymes cooperate in trimming the N-terminal residues from precursors peptides, so as to generate optimal-length antigens to fit into the MHC class I groove. Alteration or loss of ERAPs function significantly modify the repertoire of antigens presented by MHC I molecules, severely affecting the activation of both NK and CD8 + T cells. It is, therefore, conceivable that variations affecting the presentation of pathogen-derived antigens might result in an inadequate immune response and onset of disease. After the first evidence showing that ERAP1-deficient mice are not able to control Toxoplasma gondii infection, a number of studies have demonstrated that ERAPs are control factors for several infectious organisms. In this review we describe how susceptibility, development, and progression of some infectious diseases may be affected by different ERAPs variants, whose mechanism of action could be exploited for the setting of specific therapeutic approaches.
Keywords	eraps ; polymorphisms ; infection diseases ; hiv ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells

Fiona Limanaqi / Silvia Zecchini / Irma Saulle / Sergio Strizzi / Claudia Vanetti / Micaela Garziano / Gioia Cappelletti / Debora Parolin / Sonia Caccia / Daria Trabattoni / Claudio Fenizia / Mario Clerici / Mara Biasin

Biological Research, Vol 57, Iss 1, Pp 1-

2024 Volume 21

Abstract: Abstract Background Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development ... ...

Abstract	Abstract Background Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. Results Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-β, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. Conclusions Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related ...
Keywords	Interferon Stimulated Genes (ISG) ; Alpha-synuclein (SNCA) ; Alpha-synuclein multimer:monomer ratio ; Viral infection ; Epithelial lung cells ; Endothelial cells ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Salivary miRNA Profiles in COVID-19 Patients with Different Disease Severities.

Saulle, Irma / Garziano, Micaela / Cappelletti, Gioia / Limanaqi, Fiona / Strizzi, Sergio / Vanetti, Claudia / Lo Caputo, Sergio / Poliseno, Mariacristina / Santantonio, Teresa Antonia / Clerici, Mario / Biasin, Mara

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: The oral mucosa is the first site of SARS-CoV-2 entry and replication, and it plays a central role in the early defense against infection. Thus, the SARS-CoV-2 viral load, miRNAs, cytokines, and neutralizing activity (NA) were assessed in saliva and ... ...

Abstract	The oral mucosa is the first site of SARS-CoV-2 entry and replication, and it plays a central role in the early defense against infection. Thus, the SARS-CoV-2 viral load, miRNAs, cytokines, and neutralizing activity (NA) were assessed in saliva and plasma from mild (MD) and severe (SD) COVID-19 patients. Here we showed that of the 84 miRNAs analyzed, 8 were differently expressed in the plasma and saliva of SD patients. In particular: (1) miRNAs let-7a-5p, let-7b-5p, and let-7c-5p were significantly downregulated; and (2) miR-23a and b and miR-29c, as well as three immunomodulatory miRNAs (miR-34a-5p, miR-181d-5p, and miR-146) were significantly upregulated. The production of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-9, and TNFα) and chemokines (CCL2 and RANTES) increased in both the saliva and plasma of SD and MD patients. Notably, disease severity correlated with NA and immune activation. Monitoring these parameters could help predict disease outcomes and identify new markers of disease progression.
MeSH term(s)	Humans ; COVID-19/genetics ; SARS-CoV-2/genetics ; MicroRNAs/genetics ; Cytokines
Chemical Substances	MicroRNAs ; Cytokines
Language	English
Publishing date	2023-07-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310992
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