The Conventional Dendritic Cell 1 Subset Primes CD8+ T Cells and Traffics Tumor Antigen to Drive Antitumor Immunity in the Brain.

The central nervous system (CNS) antigen-presenting cell (APC) that primes antitumor CD8+ T-cell responses remains undefined. Elsewhere in the body, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain parenchyma cDC1 are extremely rare; cDCs localize to the choroid plexus and dura.

Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor.

Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesentery are features of Crohn's disease. Here, we examined the genesis of these TLOs and their impact on disease progression. Whole-mount and intravital imaging of the ileum and ileum-draining collecting lymphatic vessels (CLVs) draining to mesenteric lymph nodes from TNF mice, a model of ileitis, revealed TLO formation at valves of CLVs.

LYVE1+ macrophages of murine peritoneal mesothelium promote omentum-independent ovarian tumor growth.

Two resident macrophage subsets reside in peritoneal fluid. Macrophages also reside within mesothelial membranes lining the peritoneal cavity, but they remain poorly characterized. Here, we identified two macrophage populations (LYVE1hi MHC IIlo-hi CX3CR1gfplo/- and LYVE1lo/- MHC IIhi CX3CR1gfphi subsets) in the mesenteric and parietal mesothelial linings of the peritoneum.

Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity.

Recent studies suggest that mitochondria can be transferred between cells to support the survival of metabolically compromised cells. However, whether intercellular mitochondria transfer occurs in white adipose tissue (WAT) or regulates metabolic homeostasis in vivo remains unknown. We found that macrophages acquire mitochondria from neighboring adipocytes in vivo and that this process defines a transcriptionally distinct macrophage subpopulation.

Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression.

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.

Kir6.1-dependent K channels in lymphatic smooth muscle and vessel dysfunction in mice with Kir6.1 gain-of-function.

Key Points: Spontaneous contractions are essential for normal lymph transport and these contractions are exquisitely sensitive to the K channel activator pinacidil. K channel Kir6.1 and SUR2B subunits are expressed in mouse lymphatic smooth muscle (LSM) and form functional K channels as verified by electrophysiological techniques.

Polysaccharide Capsules Equip the Human Symbiont to Modulate Immune Responses to a Dominant Antigen in the Intestine.

Bacteria express multiple diverse capsular polysaccharides (CPSs) for protection against environmental and host factors, including the host immune system. Using a mouse TCR transgenic CD4 T cell, BθOM, that is specific for and a complete set of single CPS-expressing strains, we ask whether CPSs can modify the immune responses to specific bacterial Ags. Acapsular , which lacks all CPSs, stimulated BθOM T cells more strongly than wild-type Despite similar levels of BθOM Ag expression, many single CPS-expressing strains were antistimulatory and weakly activated BθOM T cells, but a few strains were prostimulatory and strongly activated BθOM T cells just as well or better than an acapsular strain.

Expression of factor V by resident macrophages boosts host defense in the peritoneal cavity.

Macrophages resident in different organs express distinct genes, but understanding how this diversity fits into tissue-specific features is limited. Here, we show that selective expression of coagulation factor V (FV) by resident peritoneal macrophages in mice promotes bacterial clearance in the peritoneal cavity and serves to facilitate the well-known but poorly understood "macrophage disappearance reaction." Intravital imaging revealed that resident macrophages were nonadherent in peritoneal fluid during homeostasis.

Interleukin-17 Drives Interstitial Entrapment of Tissue Lipoproteins in Experimental Psoriasis.

Lipoproteins trapped in arteries drive atherosclerosis. Extravascular low-density lipoprotein undergoes receptor uptake, whereas high-density lipoprotein (HDL) interacts with cells to acquire cholesterol and then recirculates to plasma. We developed photoactivatable apoA-I to understand how HDL passage through tissue is regulated.

Limited Macrophage Positional Dynamics in Progressing or Regressing Murine Atherosclerotic Plaques-Brief Report.

Objective- Macrophages play important roles in the pathogenesis of atherosclerosis, but their dynamics within plaques remain obscure. We aimed to quantify macrophage positional dynamics within progressing and regressing atherosclerotic plaques. Approach and Results- In a stable intravital preparation, large asymmetrical foamy macrophages in the intima of carotid artery plaques were sessile, but smaller rounded cells nearer plaque margins, possibly newly recruited monocytes, mobilized laterally along plaque borders.

The resident macrophages in murine pancreatic islets are constantly probing their local environment, capturing beta cell granules and blood particles.

Aims/hypothesis: We studied here the interactions between the resident macrophages of pancreatic islets with beta cells and the blood vasculature. We also examined the immunological consequences of such interactions.

Methods: Islets were isolated from C57BL/6 mice expressing CX3C motif chemokine receptor 1-green fluorescent protein (CX3CR-GFP) and examined live by two-photon microscopy.

Opposing Roles of Dendritic Cell Subsets in Experimental GN.

Dendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, to perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs in renal inflammation using a CD11c reporter mouse line and two mouse lines with DC-specific reporters, -GFP and -GFP.

Thermoneutrality but Not UCP1 Deficiency Suppresses Monocyte Mobilization Into Blood.

Rationale: Ambient temperature is a risk factor for cardiovascular disease. Cold weather increases cardiovascular events, but paradoxically, cold exposure is metabolically protective because of UCP1 (uncoupling protein 1)-dependent thermogenesis.

Objective: We sought to determine the differential effects of ambient environmental temperature challenge and UCP1 activation in relation to cardiovascular disease progression.

CD36 deficiency impairs the small intestinal barrier and induces subclinical inflammation in mice.

Background & Aims: CD36 has immuno-metabolic actions and is abundant in the small intestine on epithelial, endothelial and immune cells. We examined the role of CD36 in gut homeostasis using mice null for CD36 (CD36KO) and with CD36 deletion specific to enterocytes (Ent-CD36KO) or endothelial cells (EC-CD36KO).

Methods: Intestinal morphology was evaluated using immunohistochemistry and electron microscopy (EM).

Intravital and Kidney Slice Imaging of Podocyte Membrane Dynamics.

In glomerular disease, podocyte injury results in a dramatic change in cell morphology known as foot process effacement. Remodeling of the actin cytoskeleton through the activity of small GTPases was identified as a key mechanism in effacement, with increased membrane activity and motility in vitro However, whether podocytes are stationary or actively moving cells in vivo remains debated. Using intravital and kidney slice two-photon imaging of the three-dimensional structure of mouse podocytes, we found that uninjured podocytes remained nonmotile and maintained a canopy-shaped structure over time.

Heart-resident CCR2 macrophages promote neutrophil extravasation through TLR9/MyD88/CXCL5 signaling.

It is well established that maladaptive innate immune responses to sterile tissue injury represent a fundamental mechanism of disease pathogenesis. In the context of cardiac ischemia reperfusion injury, neutrophils enter inflamed heart tissue, where they play an important role in potentiating tissue damage and contributing to contractile dysfunction. The precise mechanisms that govern how neutrophils are recruited to and enter the injured heart are incompletely understood.

CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability.

Lymphatic collecting vessels direct lymph into and from lymph nodes (LNs) and can become hyperpermeable as the result of a previous infection. Enhanced permeability has been implicated in compromised immunity due to reduced flow of lymph and immune cells to LNs, which are the primary site of antigen presentation to T cells. Presently, very little is known about the molecular signals that affect lymphatic collecting vessel permeability.