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Primary immune regulation disorders lead to autoimmunity, allergy and inflammatory conditions due to defects in the immune homeostasis affecting different T, B and NK cell subsets. To improve our understanding of these conditions, in this work we analyzed the T and B cell compartments of 15 PID patients with dysregulation, including 3 patients with STAT1 GOF mutation, 7 patients with CVID with dysregulation, 3 patients with mutations in CTLA4, 1 patient with CD25 mutation and 1 patient with STAT5b mutation and compared them with healthy donors and with CVID patients without dysregulation. CD4+ and CD8+ T cells from the patients exhibited a significant decreased frequency of naïve and regulatory T cells with increased frequencies of activated cells, central memory CD4+ T cells, effector memory CD8+ T cells and terminal effector CD8+ T cells. Patients also exhibited a significantly increased frequency of circulating CD4+ follicular helper T cells, with altered frequencies of cTfh cell subsets. Such cTfh cells wcontributes to their autoimmune and inflammatory conditions. Therefore, assessment of these alterations by flow cytometry constitutes a simple and straightforward manner to improve diagnosis of these complex clinical entities that may impact early diagnosis and patients’ treatment. Also, our findings unravel phenotypic alterations that might be associated, at least in part, with some of the clinical manifestations observed in these patients.Immune evasion is an important cancer hallmark and the understanding of its mechanisms has generated successful therapeutic approaches. Induction of immunogenic cell death (ICD) is expected to attract immune cell populations that promote innate and adaptive immune responses. Here, we present a critical advance for our adenovirus-mediated gene therapy approach, where the combined p14ARF and human interferon-β (IFNβ) gene transfer to human melanoma cells led to oncolysis, ICD and subsequent activation of immune cells. Our results indicate that IFNβ alone or in combination with p14ARF was able to induce massive cell death in the human melanoma cell line SK-MEL-147, though caspase 3/7 activation was not essential. In situ gene therapy of s.c. SK-MEL-147 tumors in Nod-Scid mice revealed inhibition of tumor growth and increased survival in response to IFNβ alone or in combination with p14ARF. Emission of critical markers of ICD (exposition of calreticulin, secretion of ATP and IFNβ) was stronger when cells were treated with combined p14ARF and IFNβ gene transfer. Co-culture of previously transduced SK-MEL-147 cells with monocyte-derived dendritic cells (Mo-DCs) derived from healthy donors resulted in increased levels of activation markers HLA-DR, CD80, and CD86. Activated Mo-DCs were able to prime autologous and allogeneic T cells, resulting in increased secretion of IFNγ, TNF-α, and IL-10. Preliminary data showed that T cells primed by Mo-DCs activated with p14ARF+IFNβ-transduced SK-MEL-147 cells were able to induce the loss of viability of fresh non-transduced SK-MEL-147 cells, suggesting the induction of a specific cytotoxic population that recognized and killed SK-MEL-147 cells. Collectively, our results indicate that p14ARF and IFNβ delivered by our adenoviral system induced oncolysis in human melanoma cells accompanied by adaptive immune response activation and regulation.Frailty is a syndrome characterized by the decline in the physiologic reserve and function of several systems, leading to increased vulnerability and adverse health outcomes. While common in the elderly, recent studies have underlined the higher prevalence of frailty in chronic diseases, independent of age. The pathophysiological mechanisms that contribute to frailty have not been completely understood, although significant progresses have recently been made. In this context, chronic inflammation is likely to play a pivotal role, both directly and indirectly through other systems, such as the musculoskeletal, endocrine, and neurological systems. Rheumatic diseases are characterized by chronic inflammation and accumulation of deficits during time. Therefore, studies have recently started to explore the link between frailty and rheumatic diseases, and in this review, we report what has been described so far. Frailty is dynamic and potentially reversible with 8.3%-17.9% of older adults spontaneously improving thss likely to tolerate potentially toxic medications and might benefit from more conservative regimens. In conclusion, the implementation of the concept of frailty in rheumatology will allow a better understanding of the patient global health, a finest risk stratification and a more individualized management strategy.Invariant natural killer T (iNKT) cells represent a subclass of T cells possessing a restricted repertoire of T cell receptors enabling them to recognize lipid derived ligands. iNKT cells are continuously generated in thymus and differentiate into three main subpopulations iNKT1, iNKT2, and iNKT17 cells. We investigated the transcriptomes of these subsets comparing cells isolated from young adult (6-10 weeks old) and aged BALB/c mice (25-30 weeks of age) in order to identify genes subject to an age-related regulation of expression. These time points were selected to take into consideration the consequences of thymic involution that radically alter the existing micro-milieu. Significant differences were detected in the expression of histone genes affecting all iNKT subsets. Also the proliferative capacity of iNKT cells decreased substantially upon aging. Several genes were identified as possible candidates causing significant age-dependent changes in iNKT cell generation and/or function such as genes coding for granzyme A, ZO-1, EZH2, SOX4, IGF1 receptor, FLT4, and CD25. Moreover, we provide evidence that IL2 differentially affects homeostasis of iNKT subsets with iNKT17 cells engaging a unique mechanism to respond to IL2 by initiating a slow rate of proliferation.Chronic graft-versus-host disease (cGvHD) is one of the major complications of allogeneic stem cell transplantation (HSCT). AZ191 manufacturer cGvHD is an autoimmune-like disorder affecting multiple organs and involves a dermatological rash, tissue inflammation and fibrosis. The incidence of cGvHD has been reported to be as high as 30% to 60% and there are currently no reliable tools for predicting the occurrence of cGvHD. There is therefore an important unmet clinical need for predictive biomarkers. The present review summarizes the state of the art for genetic variation as a predictive biomarker for cGvHD. We discuss three different modes of action for genetic variation in transplantation genetic associations, genetic matching, and pharmacogenetics. The results indicate that currently, there are no genetic polymorphisms or genetic tools that can be reliably used as validated biomarkers for predicting cGvHD. A number of recommendations for future studies can be drawn. The majority of studies to date have been under-powered and included too few patients and genetic markers.