Biology subjects

Li, R.-K.

Publications and source records attributed to Li, R.-K..

3 recordsLinked to original sources

bioRxiv2026

Young bone marrow-derived microglia-like cells improve cognitive function in the aged brain through BDNF-TrkB signalling

Blood-borne macrophages are present in the brain under normal and pathological conditions. Although the complete role of these cells has yet to be determined, emerging evidence shows these cells to be vital during injury and infection, and contribute to the brain's macrophage niche throughout the entirety of an organism's lifespan. This is not always beneficial as macrophages become pro-inflammatory, primed, and hyper-activated with age and disease. One solution is to introduce macrophage precursor cells from young donors into the aged brain to attenuate age- and injury-induced inflammation and cognitive decline. Despite drastic improvements, it remains unclear by which mechanism(s) these cells rejuvenate brain function. To understand this, we generated mice whose CX3CR1-expressing macrophages are selectively depletable using diphtheria toxin. Controlled ablation of donor bone marrow (BM)-derived macrophages from the aged brain was achieved one or three months after transplanting into aged wild type recipients. At three months, the overall brain microglial-niche failed to repopulate from either peripherally- or centrally-derived macrophages after depletion. This was accompanied by severely reduced global monocyte recruitment and a large influx of neutrophils to the brain. Hippocampal-dependent behaviour was unaffected, presumably due to the absence of these cells in the hippocampus during this time point. At one month, BM-derived microglia-like cells were abundant in the hippocampus and their depletion severely impaired improvements in cognitive function and inhibited dendritic spine arborisation in hippocampal neurons. Pharmacological blocking of the brain-derived neurotrophic factor (BDNF) receptor, tropomyosin-related kinase B (TrkB), yielded the same detrimental effects in these mice as depleting the cells. These findings suggest that young BM-derived microglia-like cells could improve cognitive function in aged animals via the BDNF-TrkB signalling pathway during early brain homing and do not require permanent integration for beneficial effects to persist long-term.

immunology↗

bioRxiv2023

B Cells Promote T Cell Immunosenescence and Mammalian Aging Parameters

A dysregulated adaptive immune system is a key feature of aging, and is associated with age-related chronic diseases and mortality. Most notably, aging is linked to a loss in the diversity of the T cell repertoire and expansion of activated inflammatory age-related T cell subsets, though the main drivers of these processes are largely unknown. Here, we find that T cell aging is directly influenced by B cells. Using multiple models of B cell manipulation and single-cell omics, we find B cells to be a major cell type that is largely responsible for the age-related reduction of naive T cells, their associated differentiation towards pathogenic immunosenescent T cell subsets, and for the clonal restriction of their T cell receptor (TCR). Accordingly, we find that these pathogenic shifts can be therapeutically targeted via CD20 monoclonal antibody treatment. Mechanistically, we uncover a new role for insulin receptor signaling in influencing age-related B cell pathogenicity that in turn induces T cell dysfunction and a decline in healthspan parameters. These results establish B cells as a pivotal force contributing to age-associated adaptive immune dysfunction and healthspan outcomes, and suggest new modalities to manage aging and related multi-morbidity. One Sentence SummaryInsulin receptor signaling facilitates the induction of age associated B cell inflammatory changes, which drive phenotypic aging of the T cell compartment and adverse outcomes to mammalian healthspan parameters.

immunology↗

bioRxiv2020

Delineating the relationship between immune system aging and myogenesis in muscle repair

How aging affects the communication between immune cells and myoblasts during myogenesis is unclear. We therefore investigated how aging impacts the cellular synchronization of these two processes after muscle injury. Muscles of old mice (20 months) had chronic inflammation and fewer satellite cells compared to young mice (3 months). After injury, young mice developed a robust, but transient inflammatory response and a stepwise myogenic gene expression program. These responses were impaired with age. Replacement of old bone marrow (BM) via heterochronic bone marrow transplantation (BMT) increased muscle mass and performance on locomotive and behavioural tests. After injury, Y-O BMT restored the immune cell and cytokine profiles to a young phenotype and enhanced satellite cell activity while O-O BMT amplified a late-onset proinflammatory response. In vitro, conditioned media from young or old macrophages had no effect or impaired myoblast proliferation, respectively. Thus, BM age negatively affects myogenesis by inhibiting myoblast proliferation.

immunology↗