Failure of resolution pathways in periodontitis is reflected in levels of specialized pro-resolving lipid mediators (SPMs) and SPM pathway markers but their relationship with the subgingival microbiome is unclear. This study aimed to analyze and integrate lipid mediator level, SPM receptor gene expression and subgingival microbiome data in subjects with periodontitis vs. healthy controls. The study included 13 periodontally healthy and 15 periodontitis subjects that were evaluated prior to or after non-surgical periodontal therapy. Samples of gingival tissue and subgingival plaque were collected prior to and 8 weeks after non-surgical treatment; only once in the healthy group. Metabololipidomic analysis was performed to measure levels of SPMs and other relevant lipid mediators in gingiva. qRT-PCR assessed relative gene expression (2-ΔΔCT) of known SPM receptors. 16S rRNA sequencing evaluated the relative abundance of bacterial species in subgingival plaque. Correlations between lipid mediator levels, receptoreminatus, and four lipid mediators, 5(S)12(S)-DiHETE, RvD1, Maresin 1 and LTB4, were identified in both conditions. Four Selenomonas species were highly correlated with RvD1, RvE3, 5(S)12(S)-DiHETE and proinflammatory mediators in the periodontitis after treatment group. Profiles of lipid mediators, receptor gene and subgingival microbiome are associated with periodontal inflammation and correlated with each other, suggesting inflammation mediated by lipid mediators influences microbial composition in periodontitis. The role of correlated individual lipid mediators and bacterial species in periodontal inflammation have to be further studied.Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast-osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response layers, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. BMS-536924 mouse Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.Complement factor B (FB) mutant variants are associated with excessive complement activation in kidney diseases such as atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy and membranoproliferative glomerulonephritis (MPGN). Patients with aHUS are currently treated with eculizumab while there is no specific treatment for other complement-mediated renal diseases. In this study the phenotype of three FB missense variants, detected in patients with aHUS (D371G and E601K) and MPGN (I242L), was investigated. Patient sera with the D371G and I242L mutations induced hemolysis of sheep erythrocytes. Mutagenesis was performed to study the effect of factor D (FD) inhibition on C3 convertase-induced FB cleavage, complement-mediated hemolysis, and the release of soluble C5b-9 from glomerular endothelial cells. The FD inhibitor danicopan abrogated C3 convertase-associated FB cleavage to the Bb fragment in patient serum, and of the FB constructs, D371G, E601K, I242L, the gain-of-function mutation D279G, and the wild-type construct, in FB-depleted serum. Furthermore, the FD-inhibitor blocked hemolysis induced by the D371G and D279G gain-of-function mutants. In FB-depleted serum the D371G and D279G mutants induced release of C5b-9 from glomerular endothelial cells that was reduced by the FD-inhibitor. These results suggest that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations.With the increasing availability and accessibility of single cell technologies, much attention has been given to delineating the specific populations of cells present in any given tissue. In recent years, hepatic macrophage heterogeneity has also begun to be examined using these strategies. While previously any macrophage in the liver was considered to be a Kupffer cell (KC), several studies have recently revealed the presence of distinct subsets of hepatic macrophages, including those distinct from KCs both under homeostatic and non-homeostatic conditions. This heterogeneity has brought the concept of macrophage plasticity into question. Are KCs really as plastic as once thought, being capable of responding efficiently and specifically to any given stimuli? Or are the differential responses observed from hepatic macrophages in distinct settings due to the presence of multiple subsets of these cells? With these questions in mind, here we examine what is currently understood regarding hepatic macrophage heterogeneity in mouse and human and examine the role of heterogeneity vs plasticity in regards to hepatic macrophage responses in settings of both pathogen-induced and sterile inflammation.Since the first clinical report in 2013, inhibitors of the intracellular kinase BTK (BTKi) have profoundly altered the treatment paradigm of B cell malignancies, replacing chemotherapy with targeted agents in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström's macroglobulinemia. There are over 20 BTKi, both irreversible and reversible, in clinical development. While loss-of-function (LoF) mutations in the BTK gene cause the immunodeficiency X-linked agammaglobulinemia, neither inherited, nor somatic BTK driver mutations are known. Instead, BTKi-sensitive malignancies are addicted to BTK. BTK is activated by upstream surface receptors, especially the B cell receptor (BCR) but also by chemokine receptors, and adhesion molecules regulating B cell homing. Consequently, BTKi therapy abrogates BCR-driven proliferation and the tissue homing capacity of the malignant cells, which are being redistributed into peripheral blood. BTKi resistance can develop over time, especially in MCL and high-risk CLL patients.