Biology subjects

Blom, A.

Publications and source records attributed to Blom, A..

3 recordsLinked to original sources

bioRxiv2025

Beta-2-microglobulin stimulates neutrophil phagocytosis of bacteria and apoptotic cells

Efficient clearance of dead cells and pathogens is essential for survival and requires both the innate and adaptive immune systems. Polymorphonuclear leukocytes (PMNs, predominantly consisting of neutrophil granulocytes) constitute an important first line of defense. These highly specialized cells can phagocytose pathogens and clear apoptotic cells through efferocytosis. Beta-2-microglobulin ({beta}2m) serves as the light chain of major histocompatibility complex class I (MHC I) molecules, associating non-covalently with the heavy transmembrane chain that binds and presents antigenic peptides to CD8+ T cells. This represents the canonical role of {beta}2m. {beta}2m is also found in the granules of PMNs and is released into the extracellular space during degranulation. However, a specific function for {beta}2m in the context of PMN function or degranulation has not yet been identified. We now present evidence that {beta}2m is of importance for both phagocytosis of pathogens and efferocytosis of dead cells by PMNs. The addition of exogenous {beta}2m (50 mg/l) to PMNs in the presence of latex beads increased the phagocytic activity from 23% to 31%. Furthermore, both {beta}2m and desLys58-{beta}2m (dK58{beta}2m) enhanced phagocytosis of Gram-negative and -positive bacteria by more than 3.6-fold, though no effect was observed with zymosan bioparticles. Maintaining tissue homeostasis requires the continuous generation of new cells and the efficient clearance of apoptotic cells through efferocytosis. Treatment with {beta}2m or dK58{beta}2m led to a dose-dependent increase in efferocytosis of apoptotic Jurkat cells, reaching up to a two-fold enhancement. This effect was comparable to that obtained by GM-CSF, used as a positive control. In all cases, cytochalasin D blocked {beta}2m-mediated uptake in PMNs. These data demonstrate that {beta}2m can be of importance in phagocytosis of bacterial pathogens as part of the innate immune response and tissue homeostasis by removing dead cells by efferocytosis.

immunology↗

bioRxiv2020

Activation of bone marrow adaptive immunity in type 2 diabetes: rescue by co-stimulation modulator Abatacept

Hypothesis Type 2 diabetes (T2D) is characterized by low-grade inflammation. Here, we investigated the state of adaptive immunity in bone marrow (BM) of patients and mice with T2D. We also tested if inhibition T cell co-stimulation by Abatacept could rescue the immune profile of T2D mice.Methods Flow-cytometry and cytokine analyses were performed on BM samples from patients with or without T2D. Moreover, we studied the immune profile of db/db and control wt/db mice. A cohort of db/db mice was randomized to receive Abatacept or vehicle for 4 weeks, with endpoints being immune cell profile and indexes of insulin sensitivity and heart performance.Results T2D patients showed increased frequencies of BM CD4+ (2.8-fold, p=0.001) and CD8+ T cells (1.8-fold, p=0.01), with upregulation of the activation marker CD69 and homing receptor CCR7 in CD4+ (1.64-fold, p=0.003 and 2.27-fold, p=0.01, respectively) and CD8+ fractions (1.79-fold, p=0.05 and 1.69-fold, p=0.02, respectively). CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and levels of pro-inflammatory chemokines and cytokines. Additionally, Abatacept improved indexes of cardiac systolic function, but not insulin sensitivity.Conclusions These novel findings support the concept of BM adaptive immune activation in T2D. Modulation of T cell co-stimulation could represent an attractive and immediately available modality to dampen inappropriate activation of adaptive immune response and protect from target organ damage.Competing Interest StatementThe authors have declared no competing interest.Abbreviations(APCs)antigen-presenting cells(BM)bone marrow(BMMCs)BM mononuclear cells(CO)cardiac output(TCM)central memory(CCR7)CC-chemokine receptor 7(DCs)dendritic cells(EDV)end diastolic volume(TEM)effector memory(ND)non-diabetic control(HSPCs)hematopoietic stem/progenitor cells(SV)stroke volume(TEMRA)terminally differentiated T memory cells(T2D)type 2 diabetes mellitus(VAT)visceral adipose tissueView Full Text

immunology↗

bioRxiv2020

Over-Confluence of expanded bone marrow mesenchymal stem cells ameliorates their chondrogenic capacity in 3D cartilage tissue engineering

Cartilage tissue engineering using bone marrow-derived mesenchymal stem cells (BM-MSCs) is a growing technology for the repair of joint defects. Culturing BM-MSCs to over confluence has historically been avoided due to perceived risk to cell viability, growth inhibition and differentiation potential. Here we show that a simple change in culture practice, based on mimicking the condensation phase during embryonic cartilage development, results in biochemically and histologically superior cartilage tissue engineered constructs. Whole transcriptome analysis of the condensing cells revealed a phenotype associated with early commitment to chondrogenic precursors. This simple adjustment to the common stem cell culture technique would impact the quality of all cartilage tissue engineering modalities utilising these cells.

cell biology↗