This links BLVR-A activity to cell growth and survival pathways. BLVR-A also contains a bZip DNA binding domain and a nuclear export sequence (NES) and acts as a transcription factor to regulate the expression of immune modulatory genes. Here we will discuss the role of heme-related immune response and the potential for targeting the heme system for therapies directed toward hepatitis and cancer. Copyright © 2020 Canesin, Hejazi, Swanson and Wegiel.Drosophila hemocytes, like those of mammals, are given rise from two distinctive phases during both the embryonic and larval hematopoiesis. Embryonically derived hemocytes, mostly composed of macrophage-like plasmatocytes, are largely identified by genetic markers. However, the cellular diversity and distinct functions of possible subpopulations within plasmatocytes have not been explored in Drosophila larvae. Here, we show that larval plasmatocytes exhibit differential expressions of Hemolectin (Hml) and Peroxidasin (Pxn) during development. Moreover, removal of plasmatocytes by overexpressing pro-apoptotic genes, hid and reaper in Hml-positive plasmatocytes, feeding high sucrose diet, or wasp infestation results in increased circulating hemocytes that are Hml-negative. Interestingly these Hml-negative plasmatocytes retain Pxn expression, and animals expressing Hml-negative and Pxn-positive subtype largely attenuate growth and abrogate metabolism. Furthermore, elevated levels of a cytokine, unpaired 3, are detected when Hml-positive hemocytes are ablated, which in turn activates JAK/STAT activity in several tissues including the fat body. Finally, we observed that insulin signaling is inhibited in this background, which can be recovered by concurrent loss of upd3. Overall, this study highlights heterogeneity in Drosophila plasmatocytes and a functional plasticity of each subtype, which reaffirms extension of their role beyond immunity into metabolic regulation for cooperatively maintaining internal homeostatic balance. Copyright © 2020 Shin, Cha, Koranteng, Cho and Shim.Immunology, already a discipline in its own right, has become a major part of many different medical fields. However, its relationship to orthopedics and trauma surgery has unfortunately, and perhaps unjustly, been developing rather slowly. Discoveries in recent years have emphasized the immense breadth of communication and connection between both systems and, importantly, the highly promising therapeutic opportunities. Recent discoveries of factors originally assigned to the immune system have now also been shown to have a significant impact on bone health and disease, which has greatly changed how we approach treatment of bone pathologies. In case of bone fracture, immune cells, especially macrophages, are present throughout the whole healing process, assure defense against pathogens and discharge a complex variety of effectors to regulate bone modeling. In rheumatoid arthritis and osteoporosis, the immune system contributes to the formation of the pathological and chronic conditions. Fascinatingly, prosthesis failure is not at all solely a mechanical problem of improper strain but works in conjunction with an active contribution of the immune system as a reaction to irritant debris from material wear. Unraveling conjoined mechanisms of the immune and osseous systems heralds therapeutic possibilities for ailments of both. Contemplation of the bone as merely an unchanging support pillar is outdated and obsolete. Instead it is mandatory that this highly diverse network be incorporated in our understanding of the immune system and hematopoiesis. Copyright © 2020 Guder, Gravius, Burger, Wirtz and Schildberg.Background Alemtuzumab is a highly effective drug for the treatment of multiple sclerosis (MS), characterized by specific patterns of depletion and repopulation. As an induction-like treatment concept, two mandatory infusion courses can inhibit long-term disease activity in the majority of patients, and additional courses can successfully manage subsequent re-emergence of disease activity. Currently, there are no biomarkers to identify patients with re-emergent disease activity requiring retreatment. Methods In this study, we systematically characterized 16 MS patients commencing alemtuzumab. Clinical parameters, MRI and detailed immunoprofiling were conducted every 3 months for up to 84 months. Results Alemtuzumab led to significant decrease in clinical disease activity in all evaluated patients. Nine out of 16 patients presented with no evidence of disease activity (NEDA)-3 up to 84 months ("complete-responder"), while 7 patients demonstrated clinical or/and subclinical MRI disease activity and received alemutzumab retreatment ("partial-responder"). In both response categories, all T- and B-cell subsets were markedly depleted after alemtuzumab therapy. In particular, absolute numbers of Th1 and Th17 cells were markedly decreased and remained stable below baseline levels-this effect was particularly pronounced in complete-responders. While mean cell numbers did not differ significantly between groups, analysis of event-driven immunoprofiling demonstrated that absolute numbers of Th1 and Th17 cells showed a reproducible increase starting 6 months before relapse activity. This change appears to predict emergent disease activity when compared with stable disease. Conclusion Studies with larger patient populations are needed to confirm that frequent immunoprofiling may assist in evaluating clinical decision-making of alemtuzumab retreatment. Copyright © 2020 Akgün, Blankenburg, Marggraf, Haase and Ziemssen.Impaired synaptic integrity and function due to accumulation of amyloid β-protein (Aβ42) oligomers is thought to be a major contributor to cognitive decline in Alzheimer's disease (AD). However, the exact role of Aβ42 oligomers in synaptotoxicity and the ability of peripheral innate immune cells to rescue synapses remain poorly understood due to the metastable nature of oligomers. Here, we utilized photo-induced cross-linking to stabilize pure oligomers and study their effects vs. fibrils on synapses and protection by Aβ-phagocytic macrophages. We found that cortical neurons were more susceptible to Aβ42 oligomers than fibrils, triggering additional neuritic arborization retraction, functional alterations (hyperactivity and spike waveform), and loss of VGluT1- and PSD95-excitatory synapses. Co-culturing neurons with bone marrow-derived macrophages protected synapses against Aβ42 fibrils; moreover, immune activation with glatiramer acetate (GA) conferred further protection against oligomers. find more Mechanisms involved increased Aβ42 removal by macrophages, amplified by GA stimulation fibrils were largely cleared through intracellular CD36/EEA1+-early endosomal proteolysis, while oligomers were primarily removed via extracellular/MMP-9 enzymatic degradation.