Role of the Skin Immune System in Wound Healing.

Wound healing is a dynamic and complex process, characterized by the coordinated activities of multiple cell types, each with distinct roles in the stages of hemostasis, inflammation, proliferation, and remodeling. The cells of the immune system not only act as sentinels to monitor the skin and promote homeostasis, but they also play an important role in the process of skin wound repair. Skin-resident and recruited immune cells release cytokines and growth factors that promote the amplification of the inflammatory process.

Functional TRPA1 Channels Regulate CD56CD16 NK Cell Cytotoxicity against Tumor Cells.

Transient receptor potential ankyrin 1 (TRPA1) channels are expressed on the surface of different cell types, including immune cells. However, TRPA1's role in the context of innate and adaptive immune responses has not been fully elucidated so far. In this study, we aimed at investigating the expression and function of TRPA1 channels on NK cells.

Platelet Derivatives and the Immunomodulation of Wound Healing.

Besides their primary role in hemostasis, platelets contain a plethora of immunomodulatory molecules that profoundly affect the entire process of wound repair. Therefore, platelet derivatives, such as platelet-rich plasma or platelet lysate, have been widely employed with promising results in the treatment of chronic wounds. Platelet derivatives provide growth factors, cytokines, and chemokines targeting resident and immigrated cells belonging to the innate and adaptive immune system.

The phosphoinositide-3-kinase (PI3K)-delta inhibitor seletalisib impairs monocyte-derived dendritic cells maturation, APC function, and promotes their migration to CCR7 and CXCR4 ligands.

PI3K pathway plays a crucial role in dendritic cells (DCs) functions, as it regulates different cellular processes, such as maturation and cytokines production. However, the specific role of PI3K p110δ isoform in human DCs has not been thoroughly addressed. In this study, we analyze the effects of seletalisib, a potent and specific inhibitor of PI3K p110δ, on phenotype and antigen-presenting functions of monocyte-derived DCs undergone maturation via LPS.

Reduced Interleukin-17-Expressing Cells in Cutaneous Melanoma.

Characterization of tumor associated lymphocytes (TILs) in tumor lesions is important to obtain a clear definition of their prognostic value and address novel therapeutic opportunities. In this work, we examined the presence of T helper (Th)17 lymphocytes in cutaneous melanoma. We performed an immunohistochemical analysis of a small cohort of primary melanomas, retrospectively selected.

Platelet lysate converts M (IFNγ+LPS) macrophages in CD206 TGF-β arginase M2-like macrophages that affect fibroblast activity and T lymphocyte migration.

Macrophages, thanks to their extreme plasticity, exert critical roles in wound healing by orchestrating tissue defenses in the early inflammatory phase, and by promoting tissue regeneration and angiogenesis at a later time point. In parallel, platelets release a large number of preformed molecules that could affect immunocyte functions. Platelet-rich plasma and platelet lysate (PL) have been widely used as a therapeutic preside for ulcers, although little is known about the effects of platelet-derived biomolecules on macrophage functions during wound healing.

Platelet lysate promotes the expansion of T regulatory cells that favours in vitro wound healing by increasing keratinocyte migration and fibroblast production of extracellular matrix components.

Background: Platelet lysate (PL) contains a cocktail of growth factors and cytokines that promote tissue repair and regeneration. In vitro studies have shown that PL may affect the reparative function of keratinocytes and fibroblasts, but little is known about the effect of PL on immune cells involved in wound healing.

Objectives: To analyse the effects of PL on T cells involved in the wound repair process.

Paradoxical psoriasis induced by TNF-α blockade shows immunological features typical of the early phase of psoriasis development.

Immunomodulation with anti-TNF-α is highly effective in the treatment of various immune-mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described.

Myocardial expression of Toll-like receptor 4 predicts the response to immunosuppressive therapy in patients with virus-negative chronic inflammatory cardiomyopathy.

Aims: We sought to determine whether myocardial expression of Toll-like receptor 4 (TLR4) may predict the response to immunosuppression.

Methods And Results: Endomyocardial biopsies from 237 patients with virus-negative inflammatory cardiomyopathy treated with immunosuppression were retrospectively examined for the expression of TLR4, differentiating those patients responding to immunosuppression (n = 193) from non-responder patients (n = 44). A semiquantitative evaluation of the immunoreactivity (grading from 0 to 4) for TLR4 and human leucocyte antigen (HLA)-DR was performed together with real-time PCR and western blot for TLR4.

Increased oxidative stress contributes to cardiomyocyte dysfunction and death in patients with Fabry disease cardiomyopathy.

Cardiac dysfunction of Fabry disease (FD) has been associated with myofilament damage and cell death as result of α-galactosidase A deficiency and globotriaosylceramide accumulation. We sought to evaluate the role of oxidative stress in FD cardiomyocyte dysfunction. Myocardial tissue from 18 patients with FD was investigated for the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine by immunohistochemistry.

Pathology and function of conduction tissue in Fabry disease cardiomyopathy.

Background: Cardiac arrhythmias are common in Fabry disease (FD) and may occur in prehypertrophic cardiomyopathy suggesting an early compromise of conduction tissue (CT). Therefore, FD X-linked and CT may be variously involved in male and female patients with FD cardiomyopathy, affecting CT function.

Methods And Results: Among 74 patients with endomyocardial biopsy diagnosis of FD cardiomyopathy, 13 (6 men; 7 women; mean age, 50.

Oxidative myocardial damage in human cocaine-related cardiomyopathy.

Aims: The pathogenesis of cocaine-related cardiomyopathy (CCM) is still unclear. Oxidative damage from cocaine-generated reactive oxygen species (ROS) overcoming myocardial antioxidant reserve has been hypothesized by experimental studies.

Methods And Results: Ten (2.

CMR sensitivity varies with clinical presentation and extent of cell necrosis in biopsy-proven acute myocarditis.

Objectives: The aim of this study was to determine whether clinical presentation and type of cell death in acute myocarditis might contribute to cardiac magnetic resonance (CMR) sensitivity.

Background: Growing evidence indicates CMR is the reference noninvasive tool for the diagnosis of acute myocarditis. However, factors affecting CMR sensitivity are still unclear.

Study of genotypic and phenotypic HIV-1 dynamics of integrase mutations during raltegravir treatment: a refined analysis by ultra-deep 454 pyrosequencing.

Background: The dynamics of raltegravir-resistant variants and their impact on virologic response in 23 HIV-1-infected patients, who started a salvage raltegravir-containing regimen, were investigated.

Methods: Integrase population sequencing and Ultra-Deep-454 Pyrosequencing (UDPS) were performed on plasma samples at baseline and at raltegravir failure. All integrase mutations detected at a frequency ≥1% were considered to be reliable for the UDPS analyses.

Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes.

The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, in order to determine their relative potency and efficacy in different cellular systems of HIV infection. Raltegravir showed better protective efficacy in all cell types; MK-2048, L870,810 and IN5 showed a potent anti-HIV-1 activity in macrophages, while in lymphocytes only MK-2048 and L870,810 showed an inhibitory effect comparable to raltegravir. IN2 was a poorly effective anti-HIV-1 compound in all cellular systems.

Secondary integrase resistance mutations found in HIV-1 minority quasispecies in integrase therapy-naive patients have little or no effect on susceptibility to integrase inhibitors.

The goal of this study was to explore the presence of integrase strand transfer inhibitor (InSTI) resistance mutations in HIV-1 quasispecies present in InSTI-naïve patients and to evaluate their in vitro effects on phenotypic susceptibility to InSTIs and their replication capacities. The RT-RNase H-IN region was PCR amplified from plasma viral RNA obtained from 49 HIV-1 subtype B-infected patients (21 drug naïve and 28 failing highly active antiretroviral therapy [HAART] not containing InSTIs) and recombined with an HXB2-based backbone with RT and IN deleted. Recombinant viruses were tested against raltegravir and elvitegravir and for replication capacity.