Early atherosclerosis depends upon responses by immune cells resident in the intimal aortic wall. Specifically, the healthy intima is thought to be populated by vascular dendritic cells (DCs) that, ...during hypercholesterolemia, initiate atherosclerosis by being the first to accumulate cholesterol. Whether these cells remain key players in later stages of disease is unknown. Using murine lineage-tracing models and gene expression profiling, we reveal that myeloid cells present in the intima of the aortic arch are not DCs but instead specialized aortic intima resident macrophages (Mac
) that depend upon colony-stimulating factor 1 and are sustained by local proliferation. Although Mac
comprise the earliest foam cells in plaques, their proliferation during plaque progression is limited. After months of hypercholesterolemia, their presence in plaques is overtaken by recruited monocytes, which induce Mac
-defining genes. These data redefine the lineage of intimal phagocytes and suggest that proliferation is insufficient to sustain generations of macrophages during plaque progression.
The lymphatic vasculature is not considered a formal part of the immune system, but it is critical to immunity. One of its major roles is in the coordination of the trafficking of antigen and immune ...cells. However, other roles in immunity are emerging. Lymphatic endothelial cells, for example, directly present antigen or express factors that greatly influence the local environment. We cover these topics herein and discuss how other properties of the lymphatic vasculature, such as mechanisms of lymphatic contraction (which immunologists traditionally do not take into account), are nonetheless integral in the immune system. Much is yet unknown, and this nascent subject is ripe for exploration. We argue that to consider the impact of lymphatic biology in any given immunological interaction is a key step toward integrating immunology with organ physiology and ultimately many complex pathologies.
Abstract
Disruption of lymphatic lipid transport is linked to obesity and type 2 diabetes (T2D), but regulation of lymphatic vessel function and its link to disease remain unclear. Here we show that ...intestinal lymphatic endothelial cells (LECs) have an increasing CD36 expression from lymphatic capillaries (lacteals) to collecting vessels, and that LEC CD36 regulates lymphatic integrity and optimizes lipid transport. Inducible deletion of CD36 in LECs in adult mice (
Cd36
ΔLEC
) increases discontinuity of LEC VE-cadherin junctions in lacteals and collecting vessels.
Cd36
ΔLEC
mice display slower transport of absorbed lipid, more permeable mesenteric lymphatics, accumulation of inflamed visceral fat and impaired glucose disposal.
CD36
silencing in cultured LECs suppresses cell respiration, reduces VEGF-C-mediated VEGFR2/AKT phosphorylation and destabilizes VE-cadherin junctions. Thus, LEC CD36 optimizes lymphatic junctions and integrity of lymphatic lipid transport, and its loss in mice causes lymph leakage, visceral adiposity and glucose intolerance, phenotypes that increase risk of T2D.
Chronic inflammatory diseases such as atherosclerosis are characterized by an accumulation of macrophages. To design therapies that would reduce macrophage burden during disease, understanding the ...cellular and molecular mechanisms that regulate macrophage removal from sites of resolving inflammation is critical. Although past studies have considered the local death of macrophages or the possibility that they emigrate out of inflammatory foci, methods to quantify death or emigration have never been employed. Here, we applied quantitative competition approaches and other methods to study resolution of thioglycollate-induced peritonitis, the model in which earlier work indicated that emigration to lymph nodes accounted for macrophage removal. We show that migration to lymph nodes occurred in a CC chemokine receptor 7–independent manner but, overall, had a quantitatively minor role in the removal of macrophages. Blocking migration did not significantly delay resolution. However, when macrophages resistant to death were competed against control macrophages, contraction of the macrophage pool was delayed in the apoptosis-resistant cells. These data refute the concept that macrophages are dominantly cleared through emigration and indicate that local death controls macrophage removal. This finding alters the emphasis on which cellular processes merit targeting in chronic diseases associated with accumulation of macrophages.
•Macrophage migration to lymph nodes during acute inflammation is quantitatively minor.•Macrophages are cleared from acute inflammation by local death.
Tumors of the peripheral nervous system are classified according to the specific origin of cell differentiation. Schwannomas (neurilemmomas) are benign nerve sheath tumors slowly growing, often ...solitary, arising from the nerves' Schwann cells that are not generally associated with malignant degeneration. The cause is unknown. The authors present a case of a 37-year-old woman with a lump formation located at the anterior aspect of the knee joint, inducing a burning-like sensation around the knee and up the whole hip. The pain increased through motion of the knee joint and during palpation. Prior to these complaints, the patient does not recall any trauma or degenerative knee conditions.
Peritoneal and pleural resident macrophages in the mouse share common features and in each compartment exist as two distinct subpopulations: F4/80(+) macrophages and MHC II(+) CD11c(+) macrophages. ...F4/80(+) macrophages derive from embryonic precursors, and their maintenance is controlled by Gata6. However, the origin and regulatory factors that maintain MHC II(+) macrophages remain unknown. Here, we show that the MHC II(+) macrophages arise postnatally from CCR2-dependent precursors that resemble monocytes. Monocytes continuously replenish this subset through adulthood. Gene expression analysis identified distinct surface markers like CD226 and revealed that the transcription factor IRF4 was selectively expressed in these macrophages relative to other organs. Monocytes first entered peritoneal or pleural cavities to become MHC II(+) cells that up-regulated CD226 and CD11c later as they continued to mature. In the absence of IRF4 or after administration of oral antibiotics, MHC II(+)CD226(-)CD11c(-) monocyte-derived cells accumulated in peritoneal and pleural cavities, but CD11c(+) CD226(+) macrophages were lost. Thus, MHC II(+) resident peritoneal and pleural macrophages are continuously replenished by blood monocytes recruited to the peritoneal and pleural cavities constitutively, starting after birth, where they require IRF4 and signals likely derived from the microbiome to fully differentiate.
Atherosclerotic lesions progress through the continued recruitment of circulating blood monocytes that differentiate into macrophages within plaque. Lesion-associated macrophages are the primary ...immune cells present in plaque, where they take up cholesterol and store lipids in the form of small droplets resulting in a unique morphology termed foam cell. Recent scientific advances have used single-cell gene expression profiling, live-cell imaging, and fate mapping approaches to describe macrophage and monocyte contributions to pro- or anti-inflammatory mechanisms, in addition to functions of motility and proliferation within lesions. Yet, many questions regarding tissue-specific regulation of monocyte-to-macrophage differentiation and the contribution of recruited monocytes at stages of atherosclerotic disease progression remain unknown. In this review, we highlight recent advances regarding the role of monocyte and macrophage dynamics in atherosclerotic disease and identify gaps in knowledge that we hope will allow for advancing therapeutic treatment or prevention strategies for cardiovascular disease.
Background and Objectives: Using 3D printed models in orthopaedics and traumatology contributes to a better understanding of injury patterns regarding surgical approaches, reduction techniques, and ...fracture fixation methods. The aim of this study is to evaluate the effectiveness of a novel technique implementing 3D printed models to facilitate the optimal preoperative planning of the surgical treatment of complex acetabular fractures. Materials and Methods: Patients with complex acetabular fractures were assigned to two groups: (1) conventional group (n = 12) and (2) 3D printed group (n = 10). Both groups included participants with either a posterior column plus posterior wall fracture, a transverse plus posterior wall fracture, or a both-column acetabular fracture. Datasets from CT scanning were segmented and converted to STL format, with separated bones and fragments for 3D printing in different colors. Comparison between the two groups was performed in terms of quality of fracture reduction (good: equal to, or less than 2 mm displacement, and fair: larger than 2 mm displacement), functional assessment, operative time, blood loss, and number of intraoperative x-rays. Results: A significant decrease in operative time, blood loss, and number of intraoperative x-rays was registered in the 3D printed group versus the conventional one (p < 0.01), with 80% of the patients in the former having good fracture reduction and 20% having fair reduction. In contrast, 50% of the patients in the conventional group had good reduction and 50% had fair reduction. The functional score at 18-month follow-up was better for patients in the 3D printed group. Conclusions: The 3D printing technique can be considered a highly efficient and patient-specific approach for management of complex acetabular fractures, helping to restore patient′s individual anatomy after surgery.
Non-conventional T lymphocytes constitute a special arm of the immune system and act as sentinels against pathogens at mucosal surfaces. These non-conventional T cells (including mucosal-associated ...invariant T MAIT cells, gamma delta γδ T cells, and natural killer T NKT cells) display several innate cell-like features and are rapidly activated by the recognition of conserved, stress-induced, self, and microbial ligands. Here, we review the role of non-conventional T cells during respiratory infections, with a particular focus on the encapsulated extracellular pathogen Streptococcus pneumoniae, the leading cause of bacterial pneumonia worldwide. We consider whether MAIT cells, γδ T cells, and NKT cells might offer opportunities for preventing and/or treating human pneumococcus infections.
PDF
