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Objective miR‐21 is highly expressed in iNKT and activated T cells, but its T‐cell autonomous functions are poorly defined. We sought to investigate the role of miR‐21 in the development and functions of T and iNKT cells, representing adaptive and innate‐like populations, respectively. Methods We studied mice with a conditional deletion of miR‐21 in all mature T lymphocytes. Results Thymic and peripheral T and iNKT compartments were normal in miR‐21 KO mice. Upon activation in vitro, miR‐21 depletion reduced T‐cell survival, TH17 polarisation and, remarkably, T‐ and iNKT cell ability to respond to low‐affinity antigens, without altering their response to high‐affinity ones. Mechanistically, miR‐21 sustained CD28‐dependent costimulation pathways required to lower the T‐cell activation threshold, inhibiting its repressors in a positive feedback circuit, in turn increasing T‐cell sensitivity to antigenic stimulation and survival. Upon immunisation with the low‐affinity self‐epitope MOG35–55, miR‐21 KO mice were indeed less susceptible than WT animals to the induction of experimental autoimmune encephalomyelitis, whereas they mounted normal T‐cell responses against high‐affinity viral epitopes generated upon lymphocytic choriomeningitis virus infection. Conclusion The induction of T‐cell responses to weak antigens (signal 1) depends on CD28 costimulation (signal 2). miR‐21 sustains CD28 costimulation, decreasing the T‐cell activation threshold and increasing their sensitivity to antigenic stimulation and survival, broadening the immune surveillance range. This occurs at the cost of unleashing autoimmunity, resulting from the recognition of weak self‐antigens by autoreactive immune responses. Thus, miR‐21 fine‐tunes T‐cell response and self‐/non‐self‐discrimination., Low‐affinity antigens triggering weak TCR signalling (Signal 1) require CD28 costimulation (signal 2) to elicit T‐cell responses. In this study, we found that miR‐21 sustains the CD28 costimulation pathway, via inhibition of its repressors in a positive feedback circuit, decreasing the T‐cell activation threshold. This broadens the range of detected antigens, at the cost of unleashing autoimmunity resulting from the recognition of weak self‐antigens by autoreactive T cells. Thus, miR‐21 fine‐tunes T‐cell response and self/non‐self‐discrimination.

Chemokines are recognized as the most critical mediators for selective neutrophil recruitment during inflammatory conditions. Furthermore, they are considered fundamental regulators of neutrophil mobilization from the bone marrow (BM) to the bloodstream and for their homing back at the end of their life for apoptosis and clearance. However, chemokines are also important mediators of neutrophil effector functions including oxidative burst, degranulation, neutrophil extracellular trap (NET)osis, and production of inflammatory mediators. Neutrophils have been historically considered as a homogeneous population. In recent years, several maturation stages and subsets with different phenotypic profiles and effector functions were described both in physiological and pathological conditions such as infections, autoimmunity, and cancer. The aim of this review is to give an overview of the current evidence regarding the role of chemokines and chemokine receptors in neutrophil biology, including their possible role in neutrophil maturation, differentiation, and in defining emerging neutrophil subsets.

This paper shows a high quality artificial cognitive capability, proposing an experimental study for the implementation of an intelligent affective computing monitoring system, based on a machine learning emotion classification.Affective computing is a research direction that aspires to bring the communication between humans and machines to a new level. This is possible by enabling machines to perceive and exhibit human-like qualities (e.g., facial expressions, bodily gestures and vocal qualities) during communication [1].The study proposal is applied in psychotherapy context for the recognition of the anger emotion by the voices of both the psychotherapist and the patient, in order to lead psychotherapists to an increasingly aware use of the voice.In a broader sense, the article belongs to the area of Cognitive infocommunications (CogInfoCom), which is an interdisciplinary research field that has emerged as a synergy between infocommunications and the cognitive sciences [2]. This merging and extension of cognitive capabilities is targeted towards engineering applications in which artificial and/or natural cognitive systems are enabled to work together more effectively.

Colorectal cancer is the third cause of death in industrialized countries. Genetic susceptibility and diet are determinant of cancer risk and tumor behavior. Variation in cancer incidence among and within populations with similar dietary patterns suggests that an individual response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenomics, defined as the interaction between nutrition and an individual genome, will likely provide important clues about responders and non-responders to nutritional intervention.Epidemiological and experimental studies suggest a protective role of some normal components of daily diet (fish oil, milk, and vegetables), estrogens, and phytoestrogens in colorectal cancer. The effect of estrogen seems to be mediated by their binding to estrogen receptor beta (ER-β), one of the two estrogen receptors with high affinity for these hormones. Very recently, the demonstration of an involvement of ER-β in the development of adenomatous polyps of the colon has also been documented, suggesting the use of selective ER-β agonists in primary colorectal cancer prevention. Phytoestrogens are plant-derived compounds that structurally and functionally act as estrogen agonists in mammals. They are characterized by a higher binding affinity to ER-β as compared to estrogen receptor alpha (ER-α), the other estrogen receptor subtype. These biological characteristics explain why the administration of phytoestrogens does not produce the classical side effects associated to estrogen administration (cerebro- and cardiovascular accidents, higher incidence of endometrial and breast cancer) and makes these substances potential candidates for colorectal cancer prevention.