Biology subjects

Brdicka, T.

Publications and source records attributed to Brdicka, T..

4 recordsLinked to original sources

bioRxiv2025

HSCs and Tregs cooperate to preserve extramedullary hematopoiesis under chronic inflammation

Hematopoietic stem cells (HSCs) are localized within specialized niches of the bone marrow (BM). However, during hematological disorders or infections, the functionality of HSCs in the BM is compromised, leading to extramedullary hematopoiesis (EMH). Chronic inflammation drives EMH, yet its impact on HSCs outside the BM is poorly understood. Using a mouse model of chronic autoinflammatory disease, we demonstrated the presence of extramedullary HSCs in blood, spleen, and inflamed tails and paws. Single-cell transcriptomics revealed a unique expression profile in extramedullary HSCs, with significant upregulation of Cd53, MHCII-associated, and immunosuppressive genes. We further demonstrated that extramedullary CD53+ HSCs act as antigen-presenting cells, promoting the development of regulatory T cells (Tregs) to control chronic inflammation at extramedullary sites. Conversely, Tregs exert a protective role on extramedullary HSCs. Altogether, our findings revealed a mutually supportive relationship between a unique subset of HSCs and T cells in inflamed tissues during chronic inflammation.

immunology↗

bioRxiv2020

The role of prolines and glycine in transmembrane domain of LAT

LAT is a critical regulator of T cell development and function. It organises signalling events at the plasma membrane. However, the mechanism, which controls LAT localisation at the plasma membrane is not fully understood. Here, we studied the impact of helix-breaking amino acids, two prolines and one glycine, in the transmembrane segment on localisation and function of LAT. Using in silico analysis, confocal and superresolution imaging and flow cytometry we demonstrate that central proline residue destabilises transmembrane helix by inducing a kink. The helical structure and dynamics is further regulated by glycine and another proline residue in the luminal part of LAT transmembrane domain. Replacement of these residues with aliphatic amino acids reduces LAT dependence on palmitoylation for sorting to the plasma membrane. However, surface expression of these mutants is not sufficient to recover function of non-palmitoylated LAT in stimulated T cells. These data indicate that geometry and dynamics of LAT transmembrane segment regulate its localisation and function in immune cells.

cell biology↗

bioRxiv2019

Unraveling nanotopography of cell surface receptors

Cells communicate with their environment via surface receptors, but nanoscopic receptor organization with respect to complex cell surface morphology remains unclear. This is mainly due to a lack of accessible, robust and high-resolution methods. Here, we present an approach for mapping the topography of receptors at the cell surface with nanometer precision. The method involves coating glass coverslips with glycine, which preserves the fine membrane morphology while allowing immobilized cells to be positioned close to the optical surface. We developed an advanced and simplified algorithm for the analysis of single-molecule localization data acquired in a biplane detection scheme. These advancements enable direct and quantitative mapping of protein distribution on ruffled plasma membranes with near isotropic 3D nanometer resolution. As demonstrated successfully for CD4 and CD45 receptors, the described workflow is a straightforward quantitative technique to study molecules and their interactions at the complex surface nanomorphology of differentiated metazoan cells.

cell biology↗

bioRxiv2019

Regulation of neutrophil NADPH oxidase by PSTPIP2 affects bone damage in murine autoinflammatory osteomyelitis

Autoinflammatory diseases are characterized by dysregulation of the innate immune system leading to spontaneous inflammation. Pstpip2cmo mouse strain is a well-characterized model of this class of disorders. Due to the mutation leading to the lack of adaptor protein PSTPIP2, these animals suffer from autoinflammatory chronic multifocal osteomyelitis similar to several human syndromes. Current evidence suggests that it is driven by hyperproduction of IL-1{beta} by neutrophil granulocytes. Here we show that in addition to IL-1{beta}, PSTPIP2 also negatively regulates ROS generation by neutrophil NADPH oxidase. Pstpip2cmo neutrophils display highly elevated ROS production in response to a range of stimuli. Inactivation of NADPH oxidase in Pstpip2cmo mice did not affect IL-1{beta} levels and the autoinflammatory process was initiated with similar kinetics. However, the bone destruction was almost completely alleviated, suggesting that dysregulated NADPH oxidase activity is a key factor promoting autoinflammatory bone damage in Pstpip2cmo mice.

immunology↗