Meyerkoenig9626

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by high autoantibodies levels and multiorgan tissue damage. The current study investigated the role of CD64 in SLE patients and animal models. According to a flow cytometry study, SLE patients showed an increase in CD64 expression in circulating monocytes. There was a correlation between CD64 and SLEDAI, blood urea nitrogen levels, and anti-Sm antibodies. see more In skin lesions of lupus MRL/lpr mice, there was high IgG deposition and CD64 expression. In vitro, cytokines IL-10 and IFN-γ upregulated CD64 expression in monocytes/macrophages that was inhibited by glucocorticoids. In CD64-deficient mice, skin inflammation induced by lupus serum was reduced. Furthermore, activation of spleen tyrosine kinase (Syk), Akt, and extracellular signal-regulated kinase (Erk) was inhibited in CD64-deficient monocytes. The results suggest that CD64 could be a biomarker for observing SLE progression, as well as a mechanistic checkpoint in lupus pathogenesis.Fc-mediated immune functions have been correlated with protection in the RV144 HIV vaccine trial and are important for immunity to a range of pathogens. IgG antibodies (Abs) that form complexes with Fc receptors (FcRs) on innate immune cells can activate Fc-mediated immune functions. Genetic variation in both IgGs and FcRs have the capacity to alter IgG-FcR complex formation via changes in binding affinity and concentration. A growing challenge lies in unraveling the importance of multiple variations, especially in the context of vaccine trials that are conducted in homogenous genetic populations. Here we use an ordinary differential equation model to quantitatively assess how IgG1 allotypes and FcγR polymorphisms influence IgG-FcγRIIIa complex formation in vaccine-relevant settings. Using data from the RV144 HIV vaccine trial, we map the landscape of IgG-FcγRIIIa complex formation predicted post-vaccination for three different IgG1 allotypes and two different FcγRIIIa polymorphisms. Overall, the model illustrates how specific vaccine interventions could be applied to maximize IgG-FcγRIIIa complex formation in different genetic backgrounds. Individuals with the G1m1,17 and G1m1,3 allotypes were predicted to be more responsive to vaccine adjuvant strategies that increase antibody FcγRIIIa affinity (e.g. glycosylation modifications), compared to the G1m-1,3 allotype which was predicted to be more responsive to vaccine boosting regimens that increase IgG1 antibody titers (concentration). Finally, simulations in mixed-allotype populations suggest that the benefit of boosting IgG1 concentration versus IgG1 affinity may be dependent upon the presence of the G1m-1,3 allotype. Overall this work provides a quantitative tool for rationally improving Fc-mediated functions after vaccination that may be important for assessing vaccine trial results in the context of under-represented genetic populations.Enhancing the synthesis of microbicidal and immunomodulatory host defense peptides (HDP) is a promising host-directed antimicrobial strategy to combat a growing threat of antimicrobial resistance. Here we investigated the effect of several natural cyclooxygenase-2 (COX-2) inhibitors on chicken HDP gene regulation. Our results indicated that phenolic COX-2 inhibitors such as quercetin, resveratrol, epigallocatechin gallate, anacardic acid, and garcinol enhanced HDP gene expression in chicken HTC macrophage cell line and peripheral blood mononuclear cells (PBMCs). Moreover, these natural COX-2 inhibitors showed a strong synergy with butyrate in augmenting the expressions of multiple HDP genes in HTC cells and PBMCs. Additionally, quercetin and butyrate synergistically promoted the expressions of mucin-2 and claudin-1, two major genes involved in barrier function, while suppressing lipopolysaccharide-triggered interleukin-1β expression in HTC macrophages. Mechanistically, we revealed that NF-κB, p38 mitogen-activated protein kinase, and cyclic adenosine monophosphate signaling pathways were all involved in the avian β-defensin 9 gene induction, but histone H4 was not hyperacetylated in response to a combination of butyrate and quercetin. Because of their HDP-inducing, barrier-protective, and antiinflammatory activities, these natural COX-2 inhibitors, when combined with butyrate, may be developed as novel host-directed antimicrobial therapeutics.

Using flow cytometry, we characterized myeloid, B, and T cells in patients recently diagnosed with relapsing-remitting multiple sclerosis (RRMS) naive to disease-modifying therapies (DMTs).

This prospective case-control study was conducted in the tertiary MS center of Catania, Italy. Demographic/clinical data and peripheral bloods were collected from 52 naive patients recently diagnosed with RRMS and sex/age-matched healthy controls (HCs) in a 21 ratio. We performed flow cytometry on isolated peripheral blood mononuclear cells to assess immune cell subsets differences between RMMS patients and HCs. We explored the biomarker potential of cell subsets using receiver operating characteristic (ROC) curves and relative area under the curve (AUC) analyses.

Monocytic myeloid-derived suppressor cells (Mo-MDSCs CD14+/HLADR

) and inflammatory monocytes (CD14+CD16+) displayed higher frequencies in RRMS patients when compared with HCs (p <.05). A lower percentage of B-unswitched memory cells was observed in RRMS patients when compared with HCs (p = .026). T cells had a higher frequency of T-helper CD4+ cells and their subset, CD4+CD161+, in RRMS patients when compared with HCs (p <.001). ROC analyses revealed an AUC >70% for Mo-MDSCs CD14+/HLADR

and inflammatory CD14+CD16+, T-helper CD3+CD4+, and T-helper CD4+CD161+.

Patients with a recent RRMS diagnosis and naive to DMTs, showed peculiar myeloid, B-, and T-cell immunophenotypes.

Patients with a recent RRMS diagnosis and naive to DMTs, showed peculiar myeloid, B-, and T-cell immunophenotypes.Inflammation is an important driver of atherosclerosis. Succinate is a new extracellular inflammatory alarm released by activated macrophages. Succinate is sensed by succinate receptor 1 (Sucnr1) and then transferred to effector cells. It is worth exploring whether succinate is capable of facilitating the inflammatory response in atherosclerosis. In this study, we firstly found that arterial serum of Coronary Heart Disease (CHD) patients contained significantly higher succinate and interleukin (IL)-1β than Health control (HC) subjects, and succinate was positively correlated with IL-1β. As demonstrated by the in vitro study, succinate/hypoxia-inducible factor 1α (Hif)-1α/IL-1β signal axis existed and significantly facilitated the inflammatory program in human umbilical vein endothelial cells (HUVECs). Under the coculture, activated macrophages released succinate, which would be transferred to HUVECs via Sucnr1 and then activate Hif-1α to produce a greater amount of IL-1β. Likewise, the aortic sinus's inflammatory phenotype was found to be more significant within Apoe-/- mice that were injected with succinate. Furthermore, Sucnr1 inhibitor (NF-56-EJ40) could significantly interrupt succinate/IL-1β signal in HUVECs and macrophages. As revealed by this study, glycolytic metabolism following the release of succinate could be found in atherosclerotic pathology, and succinate would drive succinate/IL-1β signal dependent on Sucnr1 and then exacerbate inflammatory responses. Sucnr1 might be a novel target for cutting off the transduction of succinate signal to prevent the inflammation of atherosclerosis.During the ongoing COVID-19 epidemic many efforts have gone into the investigation of the SARS-CoV-2-specific antibodies as possible therapeutics. Currently, conclusions cannot be drawn due to the lack of standardization in antibody assessments. Here we describe an approach of establishing antibody characterisation in emergent times which would, if followed, enable comparison of results from different studies. The key component is a reliable and reproducible assay of wild-type SARS-CoV-2 neutralisation based on a banking system of its biological components - a challenge virus, cells and an anti-SARS-CoV-2 antibody in-house standard, calibrated to the First WHO International Standard immediately upon its availability. Consequently, all collected serological data were retrospectively expressed in an internationally comparable way. The neutralising antibodies (NAbs) among convalescents ranged from 4 to 2869 IU mL-1 in a significant positive correlation to the disease severity. Their decline in convalescents was on average 1.4-fold in a one-month period. Heat-inactivation resulted in 2.3-fold decrease of NAb titres in comparison to the native sera, implying significant complement activating properties of SARS-CoV-2 specific antibodies. The monitoring of NAb titres in the sera of immunocompromised COVID-19 patients that lacked their own antibodies evidenced the successful transfusion of antibodies by the COVID-19 convalescent plasma units with NAb titres of 35 IU mL-1 or higher.Acute myeloid leukemias (AML) comprise a wide array of different entities, which have in common a rapid expansion of myeloid blast cells leading to displacement of normal hematopoietic cells and also disruption of the microenvironment in the bone marrow niches. Based on an insight into the complex cellular interactions in the bone marrow niches in non-neoplastic conditions in general, this review delineates the complex relationship between leukemic cells and reactive cells of the tumor microenvironment (TME) in AML. A special focus is directed on niche cells and various T-cell subsets as these also provide a potential therapeutic rationale considering e.g. immunomodulation. The TME of AML on the one hand plays a vital role for sustaining and promoting leukemogenesis but - on the other hand - it also has adverse effects on abnormal blasts developing into overt leukemia hindering their proliferation and potentially removing such cells. Thus, leukemic cells need to and develop strategies in order to manipulate the TME. Interference with those strategies might be of particular therapeutic potential since mechanisms of resistance related to tumor cell plasticity do not apply to it.The presence of infiltrating CD8+ T lymphocytes in the tumor microenvironment of lung adenocarcinoma (LUAD) is correlated with improved patient prognosis, but underlying regulatory mechanisms remain unknown. To identify biomarkers to improve early diagnosis and treatment of LUAD, we downloaded 13 immune cell line-associated datasets from the GEO database. We identified CD8+ T cell-associated genes via weighted correlation network analysis. We constructed molecular subtypes based on CD8+ T cell-associated genes and constructed a multi-gene signature. We identified 252 CD8+ T cell-associated genes significantly enriched in immune function-related pathways and two molecular subtypes of LUAD (immune cluster 1 [IC1] and IC2) using our CD8+ T cell-associated gene signature. Patients with the IC2 subtype had a higher tumor mutation burden and lower immune infiltration scores, whereas those with the IC1 subtype were more sensitive to immune checkpoint inhibitors. Prioritizing the top candidate genes to construct a 10-gene signature, we validated our model using independent GSE and TCGA datasets to confirm its robustness and stable prognostic ability.