Caterina Maria Gambino

Nutrient sensing pathways as therapeutic targets for healthy ageing

ABSTRACT Introduction: In the present paper, the authors have discussed anti-aging strategies which aim to slow the aging process and to delay the onset of age-related diseases, focusing on nutrient sensing pathways (NSPs) as therapeutic targets. Indeed, several studies have already demonstrated that both in animal models and humans, dietary interventions might have a positive impact on the aging process through the modulation of these pathways. Areas covered: Achieving healthy aging is the main challenge of the twenty-first century because lifespan is increasing, but not in tandem with good health. The authors have illustrated different approaches that can act on NSPs, modulating the rate of the aging process. Expert opinion: Humanity’s lasting dream is to reverse or, at least, postpone aging. In recent years, increasing attention has been devoted to anti-aging therapies. The subject is very popular among the general public, whose imagination runs wild with all the possible tools to delay aging and to gain immortality. Some approaches discussed in the present review should be able to substantially slow down the aging process, extending our productive, youthful lives, without frailty.

Interleukin‐9 over‐expression and T helper 9 polarization in systemic sclerosis patients

T helper 9 (Th9) cells and interleukin (IL)‐9 are involved in the pathogenesis of several autoimmune diseases. The exact role of IL‐9 and Th9 cells in patients with systemic sclerosis (SSc) have not yet been studied adequately. IL‐9, IL‐9R, transcription factor PU.1 (PU.1), IL‐4, thymic stromal lymphopoietin (TSLP) and transforming growth factor (TGF)‐β expression were assessed in skin and kidney biopsies of SSc patients and healthy controls (HC) by immunohistochemistry (IHC). The cellular source of IL‐9 was also analysed by confocal microscopy analysis. Peripheral IL‐9‐producing cells were also studied by flow cytometry. The functional relevance of IL‐9 increased expression in SSc was also investigated. Our results demonstrated a strong expression of IL‐9, IL‐9R, IL‐4, TSLP and TGF‐β in skin tissues of patients with both limited and diffuse SSc. IL‐9 expression was observed mainly in the context of skin infiltrating mononuclear cells and keratinizing squamous epithelium. IL‐9 over‐expression was also observed in renal biopsies of patients with SSc. IL‐9 producing cells in the skin were identified as Th9 cells. Similarly, Th9 cells were expanded and were the major source of IL‐9 among SSc peripheral blood mononuclear cells (PBMC), their percentage being correlated directly with the modified Rodnan skin score. Infiltrating mononuclear cells, mast cells and neutrophils expressed IL‐9R. In in‐vitro studies stimulation with rIL‐9 significantly induced NET (neutrophil extracellular traps) release by dying cells (NETosis) in neutrophils, expansion of mast cells and increase of anti‐systemic scleroderma 70 (Scl70) production by B cells. Our findings suggest that Th9 cells and IL‐9 could be implicated in the pathogenesis of SSc.

Effect of Extra Virgin Olive Oil and Table Olives on the ImmuneInflammatory Responses: Potential Clinical Applications

BACKGROUND AND OBJECTIVE Extra virgin olive oil (EVOO) is the common element among the Mediterranean countries. It can be considered a nutraceutical and functional food, thanks to its bioactive compounds. It can act and modulate different processes linked to ageing and age-related diseases related to a common chronic low grade inflammation. Depending on the cultivar, the growth conditions, the period of harvesting, the productive process and time of product storage, EVOO could contain different amount of vegetal components. Of course, the same is for table olives. METHODS The aim of our review is to summarize the effects of EVOO and table olives on the immunemediated inflammatory response, focusing our attention on human studies. RESULTS Our report highlights the effect of specific molecules obtained from EVOO on the modulation of specific cytokines and anti-oxidants suggesting the importance of the daily consumption of both EVOO and table olives in the context of a Mediterranean dietary pattern. In addition, the different action on immune-inflammatory biomarkers, are depending on the olive tree cultivar. CONCLUSION Thanks to their bioactive compounds, EVOO and table olive can be considered as nutraceutical and functional foods. The beneficial effects analysed in this review will help to understand the potential application of specific olive components as therapeutic adjuvant, supplements or drugs.

Association between γ marker, human leucocyte antigens and killer immunoglobulin-like receptors and the natural course of human cytomegalovirus infection: a pilot study performed in a Sicilian population

Natural killer (NK) cells provide a major defence against human cytomegalovirus (HCMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin‐like receptors (KIRs), and human leucocyte antigen (HLA) class I molecules. Also γ marker (GM) allotypes, able to influence the NK antibody‐dependent cell‐mediated cytotoxicity, appear to be involved in the immunological control of virus infections, including HCMV. In some cases, their contribution requires epistatic interaction with other genes of the immune system, such as HLA. In the present report, with the aim of gaining insight into the immune mechanisms controlling HCMV, we have studied the possible associations among humoral and NK responses, and HCMV infections. In a previous study we assessed whether the KIR and HLA repertoire might influence the risk of developing symptomatic (n = 60) or asymptomatic (n = 60) disease after primary HCMV infection in the immunocompetent host. In the present study, the immunocompetent patients with primary symptomatic HCMV infection were genotyped for GM3/17 and GM23 allotypes, along with the 60 participants with a previous asymptomatic infection as controls. Notwithstanding the presence of missing data record, advanced missing data recovery techniques were able to show that individuals carrying the GM23 allotypes, both homozygous and heterozygous, GM17/17, HLA‐C2 and Bw4T KIR‐ligand groups are associated with the risk of developing symptomatic infection. Our findings on the role of both cellular and humoral immunity in the control of HCMV infection should be of value in guiding efforts to reduce HCMV‐associated health complications in the elderly, including immunosenescence, and in transplantation.

HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus

Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detection. The carrier frequency of the KIR2DS2 gene was significantly increased in SLE patients compared to healthy controls (73.3 versus 45.0%; OR = 3.36; 95% CI = 1.46-7.74; p = .005) suggesting a role of KIR2DS2 gene in the susceptibility to disease. We also observed a strong positive association between the presence of HLA-C1 ligands group and the disease (82.2% in SLE patients versus 41.7% in controls; OR = 6.47, 95% CI = 2.58-16.26; p < .0001). Stepwise logistic regression analysis supported the effect of the HLA-C1 ligands in SLE patients (OR = 7.06, 95% CI = 0.07-2.19; p = .002), while the KIR genes were no longer significant. Interestingly, we found that SLE patients HLA-C1 positive showed significantly decreased plasma levels of antioxidant activity marker Taurine (69.38 ± 28.49 μmol/L) compared to SLE patients HLA-C1 negative (108.37 ± 86.09 μmol/L) (p = .03). In conclusion, HLA-C1 ligands group was significantly associated with an increased risk of SLE as well as an increased oxidative stress status overall in SLE patients.

Translation of Basic Research into Clinics: Killer Immunoglobulin-like Receptors Genes in Autoimmune and Infectious Diseases

Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIRs and HLA loci are highly polymorphic, and some of their combinations have been found to protect against viral infections or to predispose to autoimmune disorders. In particular, some activating KIRs profiles may be detrimental in autoimmune pathogenesis, and specific KIRs may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control of a given pathogen. So, considering that in the pathogenesis of many autoimmune disorders and infections innate immunity plays a key role, the recent development for KIRs characterization, diseases monitoring, and treatment becomes obvious. Here, we reviewed a growing body of evidence supporting the influence of KIRs variants and their interaction with ligands in the development of the main human autoimmune and viral diseases, highlighting the main applications in clinical practice.

Sicilian centenarian offspring are more resistant to immune ageing

BackgroundImmunosenescence constitutes a major indirect cause of morbidity and mortality in the elderly. Previous analysis of immune signatures in a cohort of centenarian offspring showed an intermediate immunophenotype between age-matched and younger controls.AimsTo confirm and extend the previous studies performing further phenotypical analysis in centenarian offspring and controls.MethodsAnalysis of Treg cells, γδ T cells, mucosal-associated invariant T cells, and senescent immune T cells was performed in centenarian offspring and controls.ResultsWe report significant differences between elderly and centenarian offspring in most of the studied subsets, showing that centenarian offspring subsets present an intermediate phenotyping between elderly and younger people.ConclusionThe whole present data confirm and extend the previous results showing that centenarian offspring retain more youthful immunological parameters and that the exhaustion of the immune system is less evident than in elderly without centenarian parents, though further investigations are warranted.