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Background: The bone marrow (BM) is a major reservoir of resting memory T cells and long-lived plasma cells, capable of providing protection against recurrent infections. Whether the age-related accumulation of adipose tissue in the BM affects the functionality and maintenance of memory cells is not well understood. Methods: For the first time, we compare human femur marrow adipose tissue (fMAT) and subcutaneous white adipose tissue of the thigh (tsWAT) obtained from the same donors. Therefore, we used microarrays for comparative global gene expression analysis, and employed assays to analyse parameters of adipocyte biology, inflammation and oxidative stress. Findings: We show that fMAT adipocytes differ significantly from tsWAT adipocytes regarding specific gene expression profiles including inflammatory responses and adipogenesis/adipocyte phenotype. Concomitant with considerably lower levels of CD36, a membrane-associated protein important for long-chain fatty acid uptake that is used as maturation marker, fMAT adipocytes are smaller and contain less triglycerides. fMAT adipocytes secrete similar levels of adiponectin and leptin as tsWAT adipocytes, and express increased levels of pro-inflammatory molecules concomitant with an elevated generation of reactive oxygen species (ROS) and impaired function of plasma cells in the BM. Interpretation: Our findings suggest that fMAT is a unique type of adipose tissue containing small adipocytes with lower CD36 protein and triglyceride levels than tsWAT but high adipokine secretion. Moreover, fMAT adipocytes secrete high levels of pro-inflammatory cytokines, contributing to inflammation and impairment of plasma cell function in the BM, suggesting that fMAT has more immune regulatory functions than tsWAT. Keywords: Aging, Bone marrow adipocytes, CD36, Inflammation, ROS

Summary: Fc receptor for IgM (FcμR)-deficient mice display dysregulated function of neutrophils, dendritic cells, and B cells. The relevance of FcμR to human T cells is still unknown. We show that FcμR is mostly stored inside the cell and that surface expression is tightly regulated. Decreased surface expression on T cells from elderly individuals is associated with alterations in the methylation pattern of the FCMR gene. Binding and internalization of IgM stimulate transport of FcμR to the cell surface to ensure sustained IgM uptake. Concurrently, IgM accumulates within the cell, and the surface expression of other receptors increases, among them the T cell receptor (TCR) and costimulatory molecules. This leads to enhanced TCR signaling, proliferation, and cytokine release, in response to low, but not high, doses of antigen. Our findings indicate that FcμR is an important regulator of T cell function and reveal an additional mode of interaction between B and T cells. : Meryk et al. demonstrate that uptake of IgM mediated by FcμR expressed on T cells increases the surface expression of TCR and costimulatory molecules to facilitate T cell activation, particularly when antigen concentrations are low. Consequently, FcμR increases TCR signaling, proliferation, and cytokine release. Keywords: FcμR, IgM, T cells, TCR activation

Trying to decrease the production of Amyloid beta (Aβ) has been envisaged as a promising approach to prevent neurodegeneration in Alzheimer's disease (AD). A chronic inflammatory reaction with activated microglia cells and astrocytes is a constant feature of AD. The participation of the immune system in the disease process is further documented in several retrospective clinical studies showing an inverse relationship between the prevalence of AD and nonsteroidal anti-inflammatory drug (NSAID) therapy. Previously, we demonstrated that the combination of the proinflammatory cytokines TNFα with IFNγ induces the production of Aβ-42 and Aβ-40 in human neuronal cells. In the present study, the neuronal cell line Sk-n-sh was incubated for 12 h with the cyclooxygenase inhibitor ibuprofen and subsequently stimulated with the cytokines TNFα and IFNγ. Ibuprofen treatment decreased the secretion of total Aβ in the conditioned media of cytokine stimulated cells by 50% and prevented the accumulation of Aβ-42 and Aβ-40 in detergent soluble cell extracts. Viability of neuronal cells measured by detection of apoptosis was neither influenced by ibuprofen nor by cytokine treatment. The reduction in the production of Aβ by ibuprofen was presumably due to a decreased production of βAPP, which in contrast to the control proteins M2 pyruvate kinase, β-tubulin and the cytokine inducible ICAM-1 was detected at low concentration in ibuprofen treated cells. The data demonstrate a possible mechanism how ibuprofen may decrease the risk and delay the onset of AD.