CD49d

BACKGROUND AND AIMS: Spotty calcium deposits (SCD) represent a vulnerable plaque feature which seems to result - as based on recent invitro studies - from inflammatory vessel-wall interactions. SCD can be reliably assessed by optical coherence tomography (OCT). Their prognostic impact is yet unknown. Therefore, the aims of this translational study were to comprehensively characterize different plaque calcification patterns, to analyze the associated inflammatory mechanisms in the microenvironment of acute coronary syndrome (ACS)-causing culprit lesions (CL) and to investigate the prognostic significance of SCD in a large cohort of ACS-patients...

Fever and hypothermia represent two opposite strategies for fighting systemic inflammation. Fever results in immune activation; hypothermia is associated with energy conservation. Systemic Inflammatory Response Syndrome (SIRS) remains a significant cause of mortality worldwide. SIRS can lead to a broad spectrum of clinical symptoms but importantly, patients can develop fever or hypothermia. During infection, polymorphonuclear cells (PMNs) such as neutrophils prevent pathogen dissemination through the formation of neutrophil extracellular traps (NETs) that ensnare and kill bacteria...

We have developed a 31-color panel to define the steady-state phenotype of T cells in human peripheral blood (Table 1). The panel presented here was optimized using cryopreserved peripheral blood mononuclear cells (PBMC). The markers included in this panel were chosen in order to characterize the steady-state phenotype of T cells and includes markers (CD45RA, CD45RO, CCR7, CD95) to distinguish the main subsets (e.g., naïve, TEM , TCM , TEMRA , TSCM etc.) of CD4, CD8, and γδ T cells. This panel also includes markers for the identification of differentiation status (CD27, CD28), activation/antigen experience status (CD11a, CD49d, CD38, HLA-DR, CD56, and CD39), co-inhibitory marker expression (PD-1, TIM-3), and CD4 T helper subsets (CXCR3, CXCR5, CCR4, CCR6, Foxp3, CD25, and CD127)...

Bone marrow microenvironmental stimuli profoundly impact hematopoietic stem cell fate and biology. As G protein-coupled receptors, the bitter taste receptors (TAS2Rs) are key in transmitting extracellular stimuli into an intracellular response, within the oral cavity but also in extraoral tissues. Their expression in the bone marrow (BM)-derived cells suggests their involvement in sensing the BM microenvironmental fluctuation. In the present study, we demonstrated that umbilical cord blood (UCB)-derived CD34+ cells express fully functional TAS2Rs along with the signal transduction cascade components and their activation by the prototypical agonist, denatonium benzoate, significantly modulated genes involved in stemness maintenance and regulation of cell trafficking...

BACKGROUND: Recent studies suggest that extended interval dosing of ocrelizumab, an anti-B cell therapy, does not affect its clinical effectiveness in most patients with multiple sclerosis (MS). However, it remains to be established whether certain B cell subsets are differentially repopulated after different dosing intervals and whether these subsets relate to clinical efficacy. METHODS: We performed high-dimensional single-cell characterization of the peripheral immune landscape of patients with MS after standard (SID; n = 43) or extended interval dosing (EID; n = 37) of ocrelizumab and in non-ocrelizumab-treated (control group, CG; n = 28) patients with MS, using mass cytometry by time of flight (CyTOF)...

INTRODUCTION: Burns are defined as a traumatic injury, usually of thermal origin, that affects the epithelial and adjacent tissue and is classified according to the depth reached. Tissue repair involved in this type of injury is often a challenge both due to its severity and the multiplicity of complications. Regenerative medicine has focused on the use of low-level laser photobiomodulation therapy (LLLT) and adipose-derived stem cells (ADSC), especially in the early stages of the process, to promote better healing and shorten repair time...

BACKGROUND: Dupilumab, a monoclonal anti-IL-4Rα antibody, is approved for several type 2 mediated inflammatory diseases like asthma, atopic dermatitis, and diffuse type 2 chronic rhinosinusitis (CRS). Clinical studies had reported a transient increase in blood eosinophils during dupilumab therapy. This study aimed to assess the impact of elevated blood eosinophils on clinical outcome and to investigate the cause of high blood eosinophil levels under dupilumab therapy. METHODS: Patients suffering from diffuse type 2 CRS treated with dupilumab were examined on days 0, 28, 90, and 180 after therapy start...

INTRODUCTION: Although IgE-mediated food allergy (FA) and eosinophilic gastrointestinal disorders (EGID) are clinically distinct and treated differently, pathogenic effector Th2 (peTh2) cells are implicated in the pathogenesis of both FA and EGID. The aim of this study was to better characterize peTh2 cells in the context of FA and EGID and the overlap between these two conditions. METHODS: Peripheral blood peTh2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) were profiled by intracellular cytokine flow cytometry in the following patient cohorts: patients with FA alone (n = 8), FA and food-triggered EGID (EGID+FA+FT, n = 7), food-triggered EGID alone (EGID+FT, n = 7), EGID without FA or specific food triggers (ONLY_EGID, n = 9), and healthy volunteers (HV, n = 7)...

CD49d, the alpha chain of the VLA-4 integrin, has a negative prognostic impact in CLL treated with the BTK-inhibitors ibrutinib and acalabrutinib. Despite BTK inhibition, VLA-4 remains inside-out activated via BCR, an activation dampened by PI3K-inhibitors. Evaluation of CD49d expression in patients starting BTK-inhibitor therapy may improve their prognostic stratification.

BACKGROUND/AIM: Immune checkpoint inhibitors have improved the treatment regimen for human cancers in recent years. Particularly, inhibitors of the checkpoint molecules PD-1/PD-L1 have emerged as promising therapeutic treatments by preventing T-cell anergy and exhaustion. However, the impact of different anti-PD-1/PD-L1 checkpoint inhibitors on human monocytes remains elusive. MATERIALS AND METHODS: In this study, using the human monocyte leukemia cell line THP-1 as a model, we investigated the influence of different therapeutic anti-PD-1/PD-L1 checkpoint inhibitors on monocytic adhesion molecule expression and cytokine secretion...

PURPOSE: To determine the role of CD49d for response to Bruton's tyrosine kinase inhibitors (BTKi) in patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: In patients treated with acalabrutinib (n = 48), CD49d expression, VLA-4 integrin activation, and tumor transcriptomes of CLL cells were assessed. Clinical responses to BTKis were investigated in acalabrutinib- (n = 48; NCT02337829) and ibrutinib-treated (n = 73; NCT01500733) patients. RESULTS: In patients treated with acalabrutinib, treatment-induced lymphocytosis was comparable for both subgroups but resolved more rapidly for CD49d+ cases...

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PURPOSE: To determine the role of CD49d for response to Bruton's tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL). METHODS: In patients treated with acalabrutinib (n=48), CD49d expression, VLA-4 integrin activation, and tumor transcriptomes of CLL cells were assessed. Clinical responses to BTKis were investigated in acalabrutinib (n=48; NCT02337829), and ibrutinib (n=73; NCT01500733) treated patients. RESULTS: In patients treated with acalabrutinib, treatment induced lymphocytosis was comparable for both subgroups but resolved more rapidly for CD49d+ cases...

Iron, supplemented as iron-loaded transferrin (holotransferrin), is an essential nutrient in mammalian cell cultures, particularly for erythroid cultures. The high cost of human transferrin represents a challenge for large scale production of red blood cells (RBCs) and for cell therapies in general. We evaluated the use of deferiprone, a cell membrane-permeable drug for iron chelation therapy, as an iron carrier for erythroid cultures. Iron-loaded deferiprone (Def3 ·Fe3+ , at 52 µmol/L) could eliminate the need for holotransferrin supplementation during in vitro expansion and differentiation of erythroblast cultures to produce large numbers of enucleated RBC...

A high salt intake causes hemodynamic changes and promotes immune response through cell activation and cytokine production, leading to pro-inflammatory conditions. Transgenic Tff3 -/- knock-out mice (TFF3ko) ( n = 20) and wild-type mice (WT) ( n = 20) were each divided into the (1) low-salt (LS) group and (2) high-salt (HS) group. Ten-week-old animals were fed with standard rodent chow (0.4% NaCl) (LS) or food containing 4% NaCl (HS) for one week (7 days). Inflammatory parameters from the sera were measured by Luminex assay...

BACKGROUND: Studies have shown that the expressions and working mechanisms of Dihydrolipoamide S-acetyltransferase (DLAT) in different cancers vary. It is necessary to analyze the expressions and regulatory roles of DLAT in tumors systematically. METHODS: Online public-platform literature on the relationships between DLAT expression levels and tumor prognosis, methylation status, genetic alteration, drug sensitivity, and immune infiltration has been reviewed. The literature includes such documents as The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Tumor Immune Estimation Resource 2...

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurovascular disease produced by extravasation of blood to the subarachnoid space after rupture of the cerebral vessels. After bleeding, the immune response is activated. The role of peripheral blood mononuclear cells (PBMCs) in this response is a current subject of research. We have analysed the changes in PBMCs of patients with aSAH and their interaction with the endothelium, focusing on their adhesion and the expression of adhesion molecules. Using an in vitro adhesion assay, we observed that the adhesion of PBMCs of patients with aSAH is increased...

BACKGROUND AND OBJECTIVES: Ocrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, is highly efficient in patients with relapsing-remitting multiple sclerosis (RR-MS). We assessed early cellular immune profiles and their association with disease activity at treatment start and under therapy, which may provide new clues on the mechanisms of action of OCR and on the disease pathophysiology. METHODS: A first group of 42 patients with an early RR-MS, never exposed to disease-modifying therapy, was included in 11 centers participating to an ancillary study of the ENSEMBLE trial (NCT03085810) to evaluate the effectiveness and safety of OCR...

Sialylation is the terminal addition of sialic acid to underlying glycans and plays a prominent role in cell adhesion and immune regulation. Sialylated structures found on adhesion molecules, such as CD49d, mediate the interactions between cancer cells and the microenvironment, facilitating metastatic seeding in target organs. Chronic lymphocytic leukemia (CLL) is a clonal B-cell malignancy characterized by the accumulation of CD5- positive B cells in the peripheral blood, bone marrow and lymph nodes. CLL cells proliferate mainly in the lymph node "proliferation centers", where the microenvironment provides pro-survival signals...

Glioblastoma (GBM) is a highly aggressive malignant brain tumor currently without an effective treatment. Inspired by the recent advances in cell membrane biomimetic nanocarriers and by the key role of macrophages in GBM pathology, we developed macrophage membrane liposomes (MML) for GBM targeting. For the first time, it was assessed the role of macrophage polarization states in the effectiveness of these drug delivery systems. Interestingly, we observed that MML derived from M2 macrophages (M2 MML) presents higher uptake and increased delivery of the anticarcinogenic drug doxorubicin compared to M1 macrophage-derived nanocarriers (M1 MML) and control liposomes (CL)...