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Article ; Online: HLA-G in Allergy: Does It Play an Immunoregulatory Role?

Negrini, Simone / Contini, Paola / Murdaca, Giuseppe / Puppo, Francesco

2022 Volume 12, Page(s) 789684

Abstract: Allergy is an inflammatory process determined by a cascade of immune events characterized by T-helper 2 lymphocytes polarization leading to interleukin-4 upregulation, IgE secretion, and mast cell and eosinophil activation. HLA-G molecules, both in ... ...

Abstract	Allergy is an inflammatory process determined by a cascade of immune events characterized by T-helper 2 lymphocytes polarization leading to interleukin-4 upregulation, IgE secretion, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, are known to play a key immunoregulatory role and their involvement in allergic diseases is supported by increasing literature data. HLA-G expression and secretion is specifically induced in peripheral blood mononuclear cells of allergic patients after
MeSH term(s)	Animals ; HLA-G Antigens/immunology ; Humans ; Hypersensitivity/immunology
Chemical Substances	HLA-G Antigens
Language	English
Publishing date	2022-01-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.789684
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Article ; Online: Baseline urinary osteopontin levels are associated with the improvement of metabolic syndrome.

Moriero, Margherita / Verzola, Daniela / Bertolotto, Maria / Minetti, Silvia / Contini, Paola / Ramoni, Davide / Liberale, Luca / Pontremoli, Roberto / Viazzi, Francesca / Pende, Aldo / Pisciotta, Livia / Montecucco, Fabrizio / Carbone, Federico

Nutrition, metabolism, and cardiovascular diseases : NMCD

2024

Abstract: Background and aims: While serum osteopontin (OPN)'s established role in cardiometabolic risk is recognized, its potential as a predictor of metabolic syndrome (MetS) improvement through a urine assay has not yet been demonstrated. In this study, we ... ...

Abstract	Background and aims: While serum osteopontin (OPN)'s established role in cardiometabolic risk is recognized, its potential as a predictor of metabolic syndrome (MetS) improvement through a urine assay has not yet been demonstrated. In this study, we propose its potential predictive role over a 12-month period of standard care, with the ability to complement anthropometric measures. Methods and results: Hierarchical clustering revealed a notable association of urinary OPN (uOPN) with MetS criteria and overcame anthropometric measures in predicting the improvement at 12 months (OR of 2.74 [95% CI 1.32 to 6.29]). uOPN significantly contributed to the homogeneity of the nodes in the random forest and ultimately enhanced the performance of anthropometric measures when assessed for accuracy and area under the curve (AUC). Conclusion: Our findings offer insights into potential applications in cardiometabolic medicine for uOPN, which is easily detectable in non-invasive biological samples through an affordable assay.
Language	English
Publishing date	2024-03-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1067704-5
ISSN	1590-3729 ; 0939-4753
ISSN (online)	1590-3729
ISSN	0939-4753
DOI	10.1016/j.numecd.2024.03.028
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Article ; Online: Osteopontin is associated with neutrophil extracellular trap formation in elderly patients with severe sepsis.

Bertolotto, Maria / Verzola, Daniela / Contini, Paola / de Totero, Daniela / Tirandi, Amedeo / Ramoni, Davide / Ministrini, Stefano / Giacobbe, Daniele Roberto / Bonaventura, Aldo / Vecchié, Alessandra / Castellani, Luca / Mirabella, Michele / Arboscello, Eleonora / Liberale, Luca / Viazzi, Francesca / Bassetti, Matteo / Montecucco, Fabrizio / Carbone, Federico

European journal of clinical investigation

2024 Volume 54, Issue 4, Page(s) e14159

MeSH term(s)	Humans ; Aged ; Extracellular Traps ; Osteopontin ; Neutrophils ; Sepsis
Chemical Substances	Osteopontin (106441-73-0)
Language	English
Publishing date	2024-01-24
Publishing country	England
Document type	Letter
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.14159
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Article ; Online: Among biomarkers of neutrophil activity, matrix metalloproteinases 8 independently predicts remission of metabolic syndrome

Carbone, F. / Elia, Edoardo / Casula, Matteo / Bonaventura, Aldo / Bertolotto, Maria / Minetti, Silvia / Artom, Nathan / Camici, Giovanni G. / Contini, Paola / Pontremoli, Roberto / Viazzi, Francesca / Bertolini, Stefano / Pende, Aldo / Pisciotta, Livia / Montecucco, Fabrizio / Liberale, Luca

The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University Nutrition, Metabolism and Cardiovascular Diseases. 2023 Jan., v. 33, no. 1 p.185-193

2023

Abstract: Inflammation due to the excess of nutrient intake plays an important role in the pathophysiology of metabolic syndrome (MetS). Here, the potential influence of neutrophils and their degranulation markers on MetS improvement upon dietary and behavioral ... ...

Abstract	Inflammation due to the excess of nutrient intake plays an important role in the pathophysiology of metabolic syndrome (MetS). Here, the potential influence of neutrophils and their degranulation markers on MetS improvement upon dietary and behavioral counselling, has been investigated. Specifically, we aimed at investigating their role as potential predictors of metabolic syndrome improvements. patients with MetS (n = 127) received behavioral and dietary recommendations before follow-up at 6 months. Serum levels of matrix metalloproteinases (MMP)8, MMP9, myeloperoxidase (MPO), tissue inhibitor of MMP (TIMP)-1, TIMP-2, TIMP-3 and resistin were tested at baseline. In the whole cohort, baseline levels of proinflammatory MMP8, MMP9 and MPO increased together with the number of MetS criteria. Seventy-three (57%) patients experienced a reduction in MetS-defining criteria at follow-up. With respect to those with no improvement, such individuals showed lower weight and waist circumference at enrolment, less frequent smoking habits, higher levels of triglycerides and lower circulating MMP8. At logistic regression analysis, baseline MMP8 showed negative predictive ability (odds ratio (OR) 0.979 [0.961–0.997]; p = 0.025) against MetS improvement. Such findings hold true even when included in the backward stepwise logistic regression model confirming MMP8 as an independent predictor (OR 0.970 [0.949–0.993]; p = 0.009). Receiver operating characteristic (ROC) curve confirmed the predictive ability of MMP8 combined in a model including baseline MetS criteria and waist circumference. Bootstrap resampling analysis internally validated our findings. Improvement of MetS is independently associated with baseline low MMP-8 levels, suggesting a pivotal role for inflammation in metabolic alteration.
Keywords	biomarkers ; blood serum ; inflammation ; metabolic syndrome ; metabolism ; metalloproteinases ; myeloperoxidase ; neutrophils ; nutrient intake ; odds ratio ; pathophysiology ; regression analysis ; remission ; resistin ; waist circumference ; Matrix-metalloproteinases ; Neutrophil
Language	English
Dates of publication	2023-01
Size	p. 185-193.
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	1067704-5
ISSN	0939-4753
ISSN	0939-4753
DOI	10.1016/j.numecd.2022.10.014
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Article ; Online: Expression of membrane-bound human leucocyte antigen-G in systemic sclerosis and systemic lupus erythematosus.

Negrini, Simone / Contini, Paola / Pupo, Francesca / Greco, Monica / Murdaca, Giuseppe / Puppo, Francesco

Human immunology

2019 Volume 81, Issue 4, Page(s) 162–167

Abstract: Human leucocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex (MHC) molecule characterized by complex immunoregulatory and tolerogenic functions. Membrane-bound HLA-G is expressed on the surface of different cell ... ...

Abstract	Human leucocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex (MHC) molecule characterized by complex immunoregulatory and tolerogenic functions. Membrane-bound HLA-G is expressed on the surface of different cell populations in both physiological and pathological conditions. Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by widespread tissue fibrosis, vascular lesions and immunological alterations. Systemic lupus erythematosus is the prototypic systemic autoimmune disease affecting virtually any organ system, such as skin, joints, central nervous system, or kidneys. In SSc and SLE patients, the membrane expression of HLA-G on monocytes (0.88 ± 1.54 and 0.43 ± 0.75, respectively), CD4+ (0.42 ± 0.78 and 0.63 ± 0.48, respectively), CD8+ (2.65 ± 3.47 and 1.29 ± 1.34, respectively) and CD4+ CD8+ double-positive cells (13.87 ± 15.97 and 3.79 ± 3.11, respectively) was significantly higher than in healthy controls (0.12 ± 0.07; 0.01 ± 0.01; 0.14 ± 0.20 and 0.32 ± 0.38, respectively) (p < 0.0001). Our results show that in SSc and SLE the membrane expression of HLA-G by different subpopulations of peripheral blood mononuclear cells (PBMC) is increased, suggesting a potential role of HLA-G molecules in the complex immunological pathogenesis of these two autoimmune disorders.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers/metabolism ; Female ; HLA-G Antigens/metabolism ; Humans ; Leukocytes, Mononuclear/metabolism ; Lupus Erythematosus, Systemic/blood ; Lupus Erythematosus, Systemic/immunology ; Male ; Middle Aged ; Monocytes/metabolism ; Scleroderma, Systemic/blood ; Scleroderma, Systemic/immunology ; T-Lymphocyte Subsets/metabolism
Chemical Substances	Biomarkers ; HLA-G Antigens
Language	English
Publishing date	2019-12-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2019.12.004
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Article: Sulfavant A as the first synthetic TREM2 ligand discloses a homeostatic response of dendritic cells after receptor engagement

Gallo, Carmela / Manzo, Emiliano / Barra, Giusi / Fioretto, Laura / Ziaco, Marcello / Nuzzo, Genoveffa / d’Ippolito, Giuliana / Ferrera, Francesca / Contini, Paola / Castiglia, Daniela / Angelini, Claudia / De Palma, Raffaele / Fontana, Angelo

Cellular and molecular life sciences. 2022 July, v. 79, no. 7

2022

Abstract: OBJECTIVE: The immune response arises from a fine balance of mechanisms that provide for surveillance, tolerance, and elimination of dangers. Sulfavant A (SULF A) is a sulfolipid with a promising adjuvant activity. Here we studied the mechanism of action ...

Abstract	OBJECTIVE: The immune response arises from a fine balance of mechanisms that provide for surveillance, tolerance, and elimination of dangers. Sulfavant A (SULF A) is a sulfolipid with a promising adjuvant activity. Here we studied the mechanism of action of SULF A and addressed the identification of its molecular target in human dendritic cells (hDCs). METHODS: Adjuvant effect and immunological response to SULF A were assessed on DCs derived from human donors. In addition to testing various reporter cells, target identification and downstream signalling was supported by a reverse pharmacology approach based on antibody blocking and gene silencing, crosstalk with TLR pathways, use of human allogeneic mixed lymphocyte reaction. RESULTS: SULF A binds to the Triggering Receptor Expressed on Myeloid cells-2 (TREM2) and initiates an unconventional maturation of hDCs leading to enhanced migration activity and up-regulation of MHC and co-stimulatory molecules without release of conventional cytokines. This response involves the SYK-NFAT axis and is compromised by blockade or gene silencing of TREM2. Activation by SULF A preserved the DC functions to excite the allogeneic T cell response, and increased interleukin-10 release after lipopolysaccharide stimulation. CONCLUSION: SULF A is the first synthetic small molecule that binds to TREM2. The receptor engagement drives differentiation of an unprecedented DC phenotype (homeDCs) that contributes to immune homeostasis without compromising lymphocyte activation and immunogenic response. This mechanism fully supports the adjuvant and immunoregulatory activity of SULF A. We also propose that the biological properties of SULF A can be of interest in various physiopathological mechanisms and therapies involving TREM2.
Keywords	T-lymphocytes ; adjuvants ; antibodies ; genes ; homeostasis ; humans ; immune response ; immunomodulation ; interleukin-10 ; ligands ; lipopolysaccharides ; lymphocyte proliferation ; mechanism of action ; monitoring ; pharmacology ; phenotype
Language	English
Dates of publication	2022-07
Size	p. 369.
Publishing place	Springer International Publishing
Document type	Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04297-z
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Article ; Online: Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping and sequence analysis.

N'Guessan, Arnaud / Kailasam, Senthilkumar / Mostefai, Fatima / Poujol, Raphaël / Grenier, Jean-Christophe / Ismailova, Nailya / Contini, Paola / De Palma, Raffaele / Haber, Carsten / Stadler, Volker / Bourque, Guillaume / Hussin, Julie G / Shapiro, B Jesse / Fritz, Jörg H / Piccirillo, Ciriaco A

iScience

2023 Volume 26, Issue 8, Page(s) 107394

Abstract: Here, we exploit a deep serological profiling strategy coupled with an integrated, computational framework for the analysis of SARS-CoV-2 humoral immune responses. Applying a high-density peptide array (HDPA) spanning the entire proteomes of SARS-CoV-2 ... ...

Abstract	Here, we exploit a deep serological profiling strategy coupled with an integrated, computational framework for the analysis of SARS-CoV-2 humoral immune responses. Applying a high-density peptide array (HDPA) spanning the entire proteomes of SARS-CoV-2 and endemic human coronaviruses allowed identification of B cell epitopes and relate them to their evolutionary and structural properties. We identify hotspots of pre-existing immunity and identify cross-reactive epitopes that contribute to increasing the overall humoral immune response to SARS-CoV-2. Using a public dataset of over 38,000 viral genomes from the early phase of the pandemic, capturing both inter- and within-host genetic viral diversity, we determined the evolutionary profile of epitopes and the differences across proteins, waves, and SARS-CoV-2 variants. Lastly, we show that mutations in spike and nucleocapsid epitopes are under stronger selection between than within patients, suggesting that most of the selective pressure for immune evasion occurs upon transmission between hosts.
Language	English
Publishing date	2023-07-13
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107394
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Article ; Online: Sulfavant A as the first synthetic TREM2 ligand discloses a homeostatic response of dendritic cells after receptor engagement.

Gallo, Carmela / Manzo, Emiliano / Barra, Giusi / Fioretto, Laura / Ziaco, Marcello / Nuzzo, Genoveffa / d'Ippolito, Giuliana / Ferrera, Francesca / Contini, Paola / Castiglia, Daniela / Angelini, Claudia / De Palma, Raffaele / Fontana, Angelo

Cellular and molecular life sciences : CMLS

2022 Volume 79, Issue 7, Page(s) 369

Abstract: Objective: The immune response arises from a fine balance of mechanisms that provide for surveillance, tolerance, and elimination of dangers. Sulfavant A (SULF A) is a sulfolipid with a promising adjuvant activity. Here we studied the mechanism of ... ...

Abstract	Objective: The immune response arises from a fine balance of mechanisms that provide for surveillance, tolerance, and elimination of dangers. Sulfavant A (SULF A) is a sulfolipid with a promising adjuvant activity. Here we studied the mechanism of action of SULF A and addressed the identification of its molecular target in human dendritic cells (hDCs). Methods: Adjuvant effect and immunological response to SULF A were assessed on DCs derived from human donors. In addition to testing various reporter cells, target identification and downstream signalling was supported by a reverse pharmacology approach based on antibody blocking and gene silencing, crosstalk with TLR pathways, use of human allogeneic mixed lymphocyte reaction. Results: SULF A binds to the Triggering Receptor Expressed on Myeloid cells-2 (TREM2) and initiates an unconventional maturation of hDCs leading to enhanced migration activity and up-regulation of MHC and co-stimulatory molecules without release of conventional cytokines. This response involves the SYK-NFAT axis and is compromised by blockade or gene silencing of TREM2. Activation by SULF A preserved the DC functions to excite the allogeneic T cell response, and increased interleukin-10 release after lipopolysaccharide stimulation. Conclusion: SULF A is the first synthetic small molecule that binds to TREM2. The receptor engagement drives differentiation of an unprecedented DC phenotype (homeDCs) that contributes to immune homeostasis without compromising lymphocyte activation and immunogenic response. This mechanism fully supports the adjuvant and immunoregulatory activity of SULF A. We also propose that the biological properties of SULF A can be of interest in various physiopathological mechanisms and therapies involving TREM2.
MeSH term(s)	Cytokines/metabolism ; Dendritic Cells/metabolism ; Homeostasis ; Ligands ; Lymphocyte Activation
Chemical Substances	Cytokines ; Ligands
Language	English
Publishing date	2022-06-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04297-z
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Article ; Online: Immunoregulatory Role of HLA-G in Allergic Diseases.

Murdaca, Giuseppe / Contini, Paola / Negrini, Simone / Ciprandi, Giorgio / Puppo, Francesco

Journal of immunology research

2016 Volume 2016, Page(s) 6865758

Abstract: Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in ... ...

Abstract	Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.
MeSH term(s)	Alleles ; Allergens/immunology ; Asthma/genetics ; Asthma/immunology ; Asthma/metabolism ; Asthma/therapy ; Dermatitis, Atopic/genetics ; Dermatitis, Atopic/immunology ; Dermatitis, Atopic/metabolism ; Dermatitis, Atopic/therapy ; Female ; HLA-G Antigens/chemistry ; HLA-G Antigens/genetics ; HLA-G Antigens/immunology ; Humans ; Hypersensitivity/genetics ; Hypersensitivity/immunology ; Hypersensitivity/metabolism ; Hypersensitivity/therapy ; Immunomodulation ; Pregnancy ; Protein Isoforms ; Rhinitis, Allergic/genetics ; Rhinitis, Allergic/immunology ; Rhinitis, Allergic/metabolism ; Rhinitis, Allergic/therapy
Chemical Substances	Allergens ; HLA-G Antigens ; Protein Isoforms
Language	English
Publishing date	2016
Publishing country	Egypt
Document type	Journal Article ; Review
ZDB-ID	2817541-4
ISSN	2314-7156 ; 2314-8861
ISSN (online)	2314-7156
ISSN	2314-8861
DOI	10.1155/2016/6865758
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Article: Lipoprotein(a) Modulates Carotid Atherosclerosis in Metabolic Syndrome.

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 854624

Abstract: Background and Aim: ...

Abstract	Background and Aim:
Language	English
Publishing date	2022-06-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.854624
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