Search

Abstract 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.

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.

Background and objectives: Video-capsule endoscopy (VCE) has shown a large range (38⁻83%) of diagnostic yield in unexplained iron deficiency anemia (IDA) and obscure-occult bleeding. Therefore, we retrospectively investigated the VCE-detected spectrum and the prevalence of small bowel injuries and associated risk factors in inpatients with both of the above reported conditions. Methods: We selected inpatients with IDA (hemoglobin t-test and Fisher’s exact test for continuous and categorical variables, respectively, in univariate analysis. For multivariate analysis, we used binomial logistic regression. Results: We retrieved 109 patients (female:male ratio of 53:56; age 63.4 ± 18.9 years). Eighty patients (73.4%) showed ≥1 small bowel lesions. The Lewis score was calculated in 41 patients: 13 (31.7%) showed a mild (790, respectively) score. In univariate analysis, the small bowel transit time (6.2 ± 2.9 versus 5.2 ± 2.1 h; p = 0.049) and non-steroidal anti-inflammatory drug use for at least two weeks (17.5% versus 0%; p = 0.01) were significantly higher in subjects with injuries. These associations were not confirmed at multivariate analysis. The severity of a lesion directly correlated with proton pump inhibitor (PPI) use and duration (not confirmed in multivariate analysis). VCE can reveal the source of obscure-occult bleeding in a high percentage of unexplained IDAs. A wide spectrum of endoscopic pictures may be found. Known as well as supposed risk factors for small bowel lesions may be detected.