Background In allergic patients, clinical symptoms caused by pollen remind of symptoms triggered by viral respiratory infections, which are also the main cause of asthmatic exacerbations. In patients sensitized to birch pollen, Bet v 1 is the major symptom-causing allergen. Immune mechanisms driving Bet v 1-related responses of human blood cells have not been fully characterized. Objective To characterize the immune response to Bet v 1 in peripheral blood in patients allergic to birch pollen. Methods The peripheral blood mononuclear cells of birch-allergic (n = 24) and non-allergic (n = 47) adolescents were stimulated ex-vivo followed by transcriptomic profiling. Systems-biology approaches were employed to decipher disease-relevant gene networks and deconvolution of associated cell populations. Results Solely in birch-allergic patients, co-expression analysis revealed activation of networks of innate immunity and antiviral signalling as the immediate response to Bet v 1 stimulation. Toll-like receptors and signal transducer transcription were the main drivers of gene expression patterns. Macrophages and dendritic cells were the main cell subsets responding to Bet v 1. Conclusions and clinical relevance In birch-pollen-allergic patients, the activated innate immune networks seem to be, in part, the same as those activated during viral infections. This tendency of the immune system to read pollens as viruses may provide new insight to allergy prevention and treatment.

Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano-based systems coated with immune cells-derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.

Objective: Lymphatics play an essential pathophysiological role in promoting fluid and immune cell tissue clearance. Conversely, immune cells may influence lymphatic function and remodeling. Recently, cardiac lymphangiogenesis has been proposed as a therapeutic target to prevent heart failure after myocardial infarction (MI). We investigated the effects of gene therapy to modulate cardiac lymphangiogenesis post-MI in rodents. Second, we determined the impact of cardiac-infiltrating T cells on lymphatic remodeling in the heart. Approach and Results: Comparing adenoviral versus adeno-associated viral gene delivery in mice, we found that only sustained VEGF (vascular endothelial growth factor)-C(C156S)therapy, achieved by adeno-associated viral vectors, increased cardiac lymphangiogenesis, and led to reduced cardiac inflammation and dysfunction by 3 weeks post-MI. Conversely, inhibition of VEGF-C/-D signaling, through adeno-associated viral delivery of soluble VEGFR3 (vascular endothelial growth factor receptor 3), limited infarct lymphangiogenesis. Unexpectedly, this treatment improved cardiac function post-MI in both mice and rats, linked to reduced infarct thinning due to acute suppression of T-cell infiltration. Finally, using pharmacological, genetic, and antibody-mediated prevention of cardiac T-cell recruitment in mice, we discovered that both CD4(+)and CD8(+)T cells potently suppress, in part through interferon-gamma, cardiac lymphangiogenesis post-MI. Conclusions: We show that resolution of cardiac inflammation after MI may be accelerated by therapeutic lymphangiogenesis based on adeno-associated viral gene delivery of VEGF-C-C156S. Conversely, our work uncovers a major negative role of cardiac-recruited T cells on lymphatic remodeling. Our results give new insight into the interconnection between immune cells and lymphatics in orchestration of cardiac repair after injury.

In atherosclerosis, cholesterol accumulates in cholesterol-loaded macrophages (foam cells) forming cholesterol plaques in the arterial intima. Reverse cholesterol transport (RCT) is a mechanism in which HDL and its major structural protein apolipoprotein-A-1 (apoA-1) remove cholesterol from the foam cells and take it to the liver for its final excretion from the body in the faeces. An impaired removal of cholesterol from the foam cells is a potential contributor to a reduced RCT, which is related to a higher incidence of coronary heart disease. Chymase, a neutral protease of mast cells (MCs), is widely distributed in the connective tissue of most vertebrates and able to degrade apoA-1. After the degradation, HDL-particles are unable to interact with the ABCA-1 transporter protein on the surface of macrophages, which mediates efflux of cholesterol from the macrophage foam cells to HDL particles. It has been shown that chymase derived from rat peritoneal MCs is able to degrade apoA-1 even in the presence of blood plasma which contains natural inhibitors for chymase (α-2-macroglobulin and α-1-antichymotrypsin). In the present study we wanted to find out if mouse mast cell protease 4 (mMCP-4) isolated from peritoneal mast cells is able to maintain its enzymatic activity even in the presence of mouse serum and intraperitoneal fluid. A small molecular weight compound (S-2586) was used as a substrate. In the in vitro experiments a sonicated MC preparation that contains active chymase was used and the activity of chymase was measured in the presence of varying concentrations of plasma and intraperitoneal fluid. In the in vivo experiments we evaluate whether mast cell-dependent proteolysis of HDL particles does occur, and whether such modification inhibits their efficiency in inducing cellular cholesterol efflux in vitro. We found that both serum and intraperitoneal fluid inhibited chymase activity, serum to a higher extent. Systemic activation of MCs in mast cell-competent mice, but not in mast cell-deficient mice, in vivo led to a decreased ability of plasma and intraperitoneal fluid to act as cholesterol acceptors from cultured cholesterol-loaded macrophages. Local activation of peritoneal mast cells also blocked the cholesterol efflux-inducing effect of intraperitoneally injected human apoA-1. This work was performed at the Wihuri Research Institute. Licenses for animal work were approved by the Finnish Laboratory Animal Experiment Committee (Suomen eläinkoelautakunta, ELLA). Laboratory animals (female NMRI mice) were from the Viikki Laboratory Animal Centre of the University of Helsinki and the mast cell deficient strain of mice W-sash c-kit mutant KitW-sh/W-sh were from the Jackson Laboratory (BarHarbor, Maine). The work was supervised by the director of the Research Institute Petri Kovanen MD PhD and Miriam Lee-Rueckert PhD. Laboratory assistance was perceived from the technicians of the Wihuri Research Institute.

Aneurysmal subarachnoid hemorrhage (aSAH) is a highly fatal and morbid type of hemorrhagic strokes. Intracranial aneurysms (ICAs) rupture cause subarachnoid hemorrhage. ICAs formation, growth and rupture involves cellular and molecular inflammation. Macrophages orchestrate inflammation in the wall of ICAs. Macrophages generally polarize either into classical inflammatory (M1) or alternatively-activated anti-inflammatory (M2)-phenotype. Macrophage infiltration and polarization toward M1-phenotype increases the risk of aneurysm rupture. Strategies that deplete, inhibit infiltration, ameliorate macrophage inflammation or polarize to M2-type protect against ICAs rupture. However, clinical translational data is still lacking. This review summarizes the contribution of macrophage led inflammation in the aneurysm wall and discuss pharmacological strategies to modulate the macrophageal response during ICAs formation and rupture.