Search results for " immune tolerance"
showing 8 items of 8 documents
Decellularized tracheal prelamination implant: A proposed bilateral double organ technique
2021
Introduction In tracheal replacement transplantation, prelamination is a critical stage. Nowadays, the most widely used prelamination technique is the prethoracic fascia flap with lateral thoracic artery. We propose a flap based on the internal thoracic artery, which allows a relatively non-aggressive double organ implant, and we have tested its efficacy in decellularized tracheas. Material and methods Tracheas of albino New Zealand rabbits were decellularized following a protocol that uses detergents and cryogenization, sterilized with 1kGy gamma radiation and tutorized with a stent. Bilateral pedicled flaps made of pectoral fascia and a muscular component were harvested through a longitud…
Energetic reserves, leptin and testosterone: a refinement of the immunocompetence handicap hypothesis.
2007
Electronic supplementary material is available at http://dx.doi.org/10.1098/rsbl.2007.0020 or via http://www.journals.royalsoc.ac.uk.
Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation
2009
Abstract The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell–derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17–producing T cel…
Differential impact of high and low penetrance TNFRSF1A gene mutations on conventional and regulatory CD4+ T cell functions in TNFR1-associated perio…
2015
Abstract TNFR-associated periodic syndrome is an autoinflammatory disorder caused by autosomal-dominant mutations in TNFRSF1A, the gene encoding for TNFR superfamily 1A. The lack of knowledge in the field of TNFR-associated periodic syndrome biology is clear, particularly in the context of control of immune self-tolerance. We investigated how TNF-α/TNFR superfamily 1A signaling can affect T cell biology, focusing on conventional CD4+CD25− and regulatory CD4+CD25+ T cell functions in patients with TNFR-associated periodic syndrome carrying either high or low penetrance TNFRSF1A mutations. Specifically, we observed that in high penetrance TNFR-associated periodic syndrome, at the molecular le…
Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10+ phenotype
2017
Mast cells (MCs) are innate immune cells that exert positive and negative immune modulatory functions capable to enhance or limit the intensity and/or duration of adaptive immune responses. Although MCs are crucial to regulate T cell immunity, their action in the pathogenesis of autoimmune diseases is still debated. Here we demonstrate that MCs play a crucial role in T1D pathogenesis so that their selective depletion in conditional MC knockout NOD mice protects them from the disease. MCs of diabetic NOD mice are overly inflammatory and secrete large amounts of IL-6 that favors differentiation of IL-17-secreting T cells at the site of autoimmunity. Moreover, while MCs of control mice acquire…
Common extracellular matrix regulation of myeloid cell activity in the bone marrow and tumor microenvironments
2017
The complex interaction between cells undergoing transformation and the various stromal and immunological cell components of the tumor microenvironment (TME) crucially influences cancer progression and diversification, as well as endowing clinical and prognostic significance. The immunosuppression characterizing the TME depends on the recruitment and activation of different cell types including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Less considered is the non-cellular component of the TME. Here, we focus on the extracellular matrix (ECM) regulatory activities that, within the TME, actively contribute to many aspects of tumor progression, acti…
Immune tolerance induction with moroctocog-alpha (Refacto/Refacto AF) in a population of Italian haemophilia A patients with high-titre inhibitors: D…
2019
Background: The appearance of inhibitors is the most serious complication in haemophilia A (HA) patients. The primary objective is their eradication. Up to date, immune tolerance induction (ITI) was the only therapeutic option to achieve this. Aim: To assess the efficacy of moroctocog-alpha as an ITI regimen in a population of HA patients with high-titre inhibitors. Methods: The REF.IT Registry is a retrospective-prospective study that collected data on all patients with HA and high-titre inhibitors treated with moroctocog-alpha as an ITI regimen at twelve Italian Haemophilia Centres. Results: We enrolled 27 patients, 85.2% were children. All patients were high responders, 88.9% had severe …
Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives
2020
The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in re…