Origin and differentiation of lymph node and spleen progenitors during embryonic development.

Secondary lymphoid tissues, including the spleen and lymph nodes, play an essential role in supporting immune responses. These organs are structurally organized into specialized compartments in which the interactions between hematopoietic and stromal cells are crucial for immune cell function. In this Review, we examine the cellular and molecular mechanisms that control spleen and lymph nodes, primarily in mice, with a particular emphasis on the embryonic origins of the different cell types involved.

SciGeneX: enhancing transcriptional analysis through gene module detection in single-cell and spatial transcriptomics data.

The standard pipeline to analyze single-cell RNA-seq or spatial transcriptomics data focuses on a gene-centric approach that overlooks the collective behavior of genes. However, understanding cell populations necessitates recognizing intricate combinations of activated and repressed pathways. Therefore, a broader view of gene behavior offers more accurate insights into cellular heterogeneity in single-cell or spatial transcriptomics data.

SMAC mimetic drives microglia phenotype and glioblastoma immune microenvironment.

Tumor-associated macrophages/microglia (TAMs) are highly plastic and heterogeneous immune cells that can be immune-supportive or tumor-supportive depending of the microenvironment. TAMs are the most abundant immune cells in glioblastoma (GB), and play a key role in immunosuppression. Therefore, TAMs reprogramming toward immune-supportive cells is a promising strategy to overcome immunosuppression.

Three-Dimensional Imaging of Macrophages in Complete Organs.

The introduction of the light-sheet microscope has facilitated the analysis of complete tissues for the presence of all cells and their location in relation to their niche. This contributes to a better understanding of cellular locations and interactions in organs. In the last decade, many new and improved protocols have been published which are essential to improve staining and visualization of the immune-fluorescence within different tissues.

Layered origins of lymphoid tissue inducer cells.

The Innate Lymphoid Cell (ILC) family is a relatively recently described immune cell family involved in innate immune responses and tissue homeostasis. Lymphoid Tissue Inducer (LTi) cells are part of the type 3 (ILC3) family. The ILC3 family is the main ILC population within the embryo, in which the LTi cells are critically associated with embryonic lymph node formation.

Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke.

Background: The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too.

Volumetric imaging reveals VEGF-C-dependent formation of hepatic lymph vessels in mice.

The liver is a major biosynthetic and detoxifying organ in vertebrates, but also generates 25%-50% of the lymph passing through the thoracic duct and is thereby the organ with the highest contribution to lymph flow. In contrast to its metabolic function, the role of the liver for lymph generation and composition is presently severely understudied. We took a rigorous, volume imaging-based approach to describe the microarchitecture and spatial composition of the hepatic lymphatic vasculature with cellular resolution in whole mount immune stained specimen ranging from thick sections up to entire mouse liver lobes.

Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer.

Neuronal nerve processes in the tumor microenvironment were highlighted recently. However, the origin of intra-tumoral nerves remains poorly known, in part because of technical difficulties in tracing nerve fibers via conventional histological preparations. Here, we employ three-dimensional (3D) imaging of cleared tissues for a comprehensive analysis of sympathetic innervation in a murine model of pancreatic ductal adenocarcinoma (PDAC).

Innate Lymphoid Cells in the Central Nervous System.

Immune cells are present within the central nervous system and play important roles in neurological inflammation and disease. As relatively new described immune cell population, Innate Lymphoid Cells are now increasingly recognized within the central nervous system and associated diseases. Innate Lymphoid Cells are generally regarded as tissue resident and early responders, while conversely within the central nervous system at steady-state their presence is limited.

1-deoxysphingolipids bind to COUP-TF to modulate lymphatic and cardiac cell development.

Identification of physiological modulators of nuclear hormone receptor (NHR) activity is paramount for understanding the link between metabolism and transcriptional networks that orchestrate development and cellular physiology. Using libraries of metabolic enzymes alongside their substrates and products, we identify 1-deoxysphingosines as modulators of the activity of NR2F1 and 2 (COUP-TFs), which are orphan NHRs that are critical for development of the nervous system, heart, veins, and lymphatic vessels. We show that these non-canonical alanine-based sphingolipids bind to the NR2F1/2 ligand-binding domains (LBDs) and modulate their transcriptional activity in cell-based assays at physiological concentrations.

Lymphoid Tissue inducer (LTi) cell ontogeny and functioning in embryo and adult.

Innate Lymphoid Cells (ILC) are involved in homeostasis and immunity. Their dynamic differentiation and characterization depend on their tissue of residency and is adapted to their role within these tissues. Lymphoid Tissue inducer (LTi) cells are an ILC member and essential for embryonic lymph node (LN) formation.

Distinct Waves from the Hemogenic Endothelium Give Rise to Layered Lymphoid Tissue Inducer Cell Ontogeny.

During embryogenesis, lymphoid tissue inducer (LTi) cells are essential for lymph node organogenesis. These cells are part of the innate lymphoid cell (ILC) family. Although their earliest embryonic hematopoietic origin is unclear, other innate immune cells have been shown to be derived from early hemogenic endothelium in the yolk sac as well as the aorta-gonad-mesonephros.

Expression of the Atypical Chemokine Receptor ACKR4 Identifies a Novel Population of Intestinal Submucosal Fibroblasts That Preferentially Expresses Endothelial Cell Regulators.

Atypical chemokine receptors (ACKRs) are expressed by discrete populations of stromal cells at specific anatomical locations where they control leukocyte migration by scavenging or transporting chemokines. ACKR4 is an atypical receptor for CCL19, CCL21, and CCL25. In skin, ACKR4 plays indispensable roles in regulating CCR7-dependent APC migration, and there is a paucity of migratory APCs in the skin-draining lymph nodes of -deficient mice under steady-state and inflammatory conditions.

SunRiSE - measuring translation elongation at single-cell resolution by means of flow cytometry.

The rate at which ribosomes translate mRNAs regulates protein expression by controlling co-translational protein folding and mRNA stability. Many factors regulate translation elongation, including tRNA levels, codon usage and phosphorylation of eukaryotic elongation factor 2 (eEF2). Current methods to measure translation elongation lack single-cell resolution, require expression of multiple transgenes and have never been successfully applied Here, we show, by using a combination of puromycilation detection and flow cytometry (a method we call 'SunRiSE'), that translation elongation can be measured accurately in primary cells in pure or heterogenous populations isolated from blood or tissues.

CXCL12-mediated feedback from granule neurons regulates generation and positioning of new neurons in the dentate gyrus.

Adult hippocampal neurogenesis is implicated in learning and memory processing. It is tightly controlled at several levels including progenitor proliferation as well as migration, differentiation and integration of new neurons. Hippocampal progenitors and immature neurons reside in the subgranular zone (SGZ) and are equipped with the CXCL12-receptor CXCR4 which contributes to defining the SGZ as neurogenic niche.

An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation.

Rationale: Lymphatic vessel formation and function constitutes a physiologically and pathophysiologically important process, but its genetic control is not well understood.

Objective: Here, we identify the secreted Polydom/Svep1 protein as essential for the formation of the lymphatic vasculature. We analyzed mutants in mice and zebrafish to gain insight into the role of Polydom/Svep1 in the lymphangiogenic process.

The evolution of innate lymphoid cells.

Innate lymphoid cells (ILCs) are the most recently discovered group of immune cells. Understanding their biology poses many challenges. We discuss here the current knowledge on the appearance of ILC subsets during evolution and propose how the connection between ILCs and T cells contributes to the robustness of immunity and hence to the fitness of the hosts.

Differentiation and function of group 3 innate lymphoid cells, from embryo to adult.

Group 3 innate lymphoid cells (ILC3) represent a heterogeneous population of cells that share the nuclear hormone receptor RORγt (retinoic acid receptor-related orphan receptor γt) as a master regulator for differentiation and function. ILC3 can be divided into two major subsets based on the cell surface expression of the natural cytotoxicity receptor (NCR), NKp46. A subset of NCR(-) ILC3 includes the previously known lymphoid-tissue inducer cells that are essential for the embryonic formation of peripheral lymph nodes and Peyer's patches.

Identification of natural RORγ ligands that regulate the development of lymphoid cells.

Mice deficient in the nuclear hormone receptor RORγt have defective development of thymocytes, lymphoid organs, Th17 cells, and type 3 innate lymphoid cells. RORγt binds to oxysterols derived from cholesterol catabolism, but it is not clear whether these are its natural ligands. Here, we show that sterol lipids are necessary and sufficient to drive RORγt-dependent transcription.

Involvement of neurons and retinoic acid in lymphatic development: new insights in increased nuchal translucency.

Objective: Increased nuchal translucency originates from disturbed lymphatic development. Abnormal neural crest cell (NCC) migration may be involved in lymphatic development. Because both neuronal and lymphatic development share retinoic acid (RA) as a common factor, this study investigated the involvement of NCCs and RA in specific steps in lymphatic endothelial cell (LEC) differentiation and nuchal edema, which is the morphological equivalent of increased nuchal translucency.

Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity.

The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells.

Development of secondary lymphoid organs in relation to lymphatic vasculature.

Although the initial event in lymphatic endothelial specification occurs slightly before the initiation of lymph node formation in mice, the development of lymphatic vessels and lymph nodes occurs within the same embryonic time frame. Specification of lymphatic endothelial cells starts around embryonic day 10 (E10), followed by endothelial cell budding and formation of the first lymphatic structures. Through lymphatic endothelial cell sprouting these lymph sacs give rise to the lymphatic vasculature which is complete by E15.

New insights into the development of lymphoid tissues.

Secondary lymphoid organs are important locations for the initiation of adaptive immune responses. They develop before birth, and their formation requires interaction between lymphotoxin-α₁ß₂-expressing lymphoid-tissue inducer cells and lymphotoxin-ß receptor-expressing stromal organizer cells. Here, we discuss new insights into the earliest phases of peripheral lymph node and Peyer's patch formation that occur before lymphotoxin-ß receptor signalling and suggest a role for the developing nervous system.

Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model.

Background: Bone spicule pigments (BSP) are a hallmark of retinitis pigmentosa (RP). In this study, we examined the process of BSP formation in the rhodopsin knockout (rho (-/-)) mouse, a murine model for human RP.

Methods: In rho (-/-) mice from 2 to 16 months of age, representing the range from early to late stages of degeneration, retinal sections and whole mounts were examined morphologically by light and electron microscopy.