Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neural signaling in the spleen controls B-cell responses to blood-borne antigen.

ABSTRACT: Entry of blood-borne pathogens into the spleen elicits a series of changes in cellular architecture that culminates in the systemic release of protective antibodies. Despite an abundance of work that has characterized these processes, the regulatory mechanisms that coordinate cell trafficking and antibody production are still poorly understood. Here, marginal zone (MZ) B cells responding to streptococcus in the blood were observed to migrate along splenic nerves, arriving at the red pulp venous sinuses where they become antibody-secreting cells. Electrical stimulation of the vagus nerve, which in turn regulates the splenic nerve, arrested B-cell migration and decreased antibody secretion. Thus, neural circuits regulate the first wave of antibody production following B-cell exposure to blood-borne antigen.

SUBMITTER: Mina-Osorio P

PROVIDER: S-EPMC3388134 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Neural signaling in the spleen controls B-cell responses to blood-borne antigen.

Mina-Osorio Paola P Rosas-Ballina Mauricio M Valdes-Ferrer Sergio I SI Al-Abed Yousef Y Tracey Kevin J KJ Diamond Betty B

Molecular medicine (Cambridge, Mass.) 20120509

Entry of blood-borne pathogens into the spleen elicits a series of changes in cellular architecture that culminates in the systemic release of protective antibodies. Despite an abundance of work that has characterized these processes, the regulatory mechanisms that coordinate cell trafficking and antibody production are still poorly understood. Here, marginal zone (MZ) B cells responding to streptococcus in the blood were observed to migrate along splenic nerves, arriving at the red pulp venous ...[more]

PMID: 22354214

Similar Datasets

Blood-borne macrophage-neural cell interactions hitchhike on endosome networks for cell-based nanozyme brain delivery.

Project description:Macrophage-carried nanoformulated catalase ('nanozyme') attenuates neuroinflammation and protects nigrostriatal neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication. This is facilitated by effective enzyme transfer from blood-borne macrophages to adjacent endothelial cells and neurons leading to the decomposition of reactive oxygen species.We examined the intra- and inter-cellular trafficking mechanisms of nanozymes by confocal microscopy. Improved neuronal survival mediated by nanozyme-loaded macrophages was demonstrated by fluorescence-activated cell sorting.In macrophages, nanozymes were internalized mainly by clathrin-mediated endocytosis then trafficked to recycling endosomes. The enzyme is subsequently released in exosomes facilitated by bridging conduits. Nanozyme transfer from macrophages to adjacent cells by endocytosis-independent mechanisms diffusing broadly throughout the recipient cells. In contrast, macrophage-free nanozymes were localized in lysosomes following endocytic entry.Facilitated transfer of nanozyme from cell to cell can improve neuroprotection against oxidative stress commonly seen during neurodegenerative disease processes.

| S-EPMC3384770 | biostudies-literature

Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development.

Project description:The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome P450 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insights into the molecular determinants of human congenital asplenia.

| S-EPMC4922703 | biostudies-literature

EphB signaling controls lineage plasticity of adult neural stem cell niche cells.

Project description:Stem cells remain in specialized niches over the lifespan of the organism in many organs to ensure tissue homeostasis and enable regeneration. How the niche is maintained is not understood, but is probably as important as intrinsic stem cell self-renewal capacity for tissue integrity. We here demonstrate a high degree of phenotypic plasticity of the two main niche cell types, ependymal cells and astrocytes, in the neurogenic lateral ventricle walls in the adult mouse brain. In response to a lesion, astrocytes give rise to ependymal cells and ependymal cells give rise to niche astrocytes. We identify EphB2 forward signaling as a key pathway regulating niche cell plasticity. EphB2 acts downstream of Notch and is required for the maintenance of ependymal cell characteristics, thereby inhibiting the transition from ependymal cell to astrocyte. Our results show that niche cell identity is actively maintained and that niche cells retain a high level of plasticity.

| S-EPMC3003830 | biostudies-literature

Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair.

Project description:C1q plays a key role as a recognition molecule in the immune system, driving autocatalytic complement cascade activation and acting as an opsonin. We have previously reported a non-immune role of complement C1q modulating the migration and fate of human neural stem cells (hNSC); however, the mechanism underlying these effects has not yet been identified. Here, we show for the first time that C1q acts as a functional hNSC ligand, inducing intracellular signaling to control cell behavior. Using an unbiased screening strategy, we identified five transmembrane C1q signaling/receptor candidates in hNSC (CD44, GPR62, BAI1, c-MET, and ADCY5). We further investigated the interaction between C1q and CD44 , demonstrating that CD44 mediates C1q induced hNSC signaling and chemotaxis in vitro, and hNSC migration and functional repair in vivo after spinal cord injury. These results reveal a receptor-mediated mechanism for C1q modulation of NSC behavior and show that modification of C1q receptor expression can expand the therapeutic window for hNSC transplantation.

| S-EPMC7476762 | biostudies-literature

Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling.

Project description:Themis (thymocyte-expressed molecule involved in selection), a member of a family of proteins with unknown functions, is highly conserved among vertebrates. Here we found that Themis had high expression in thymocytes between the pre-T cell antigen receptor (pre-TCR) and positive-selection checkpoints and low expression in mature T cells. Themis-deficient thymocytes showed defective positive selection, which resulted in fewer mature thymocytes. Negative selection was also impaired in Themis-deficient mice. A greater percentage of Themis-deficient T cells had CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory phenotypes than did wild-type T cells. In support of the idea that Themis is involved in TCR signaling, this protein was phosphorylated quickly after TCR stimulation and was needed for optimal TCR-driven calcium mobilization and activation of the kinase Erk.

| S-EPMC2757056 | biostudies-literature

Blood-borne soluble protein antigen intensifies T cell activation in autoimmune CNS lesions and exacerbates clinical disease.

Project description:We explored the effect of i.v. soluble antigen on autoaggressive, myelin basic protein-specific effector T cells within their target organ during acute experimental autoimmune encephalomyelitis (EAE). Intravital two-photon imaging revealed that i.v. autoantigen reached the CNS and was taken up and processed by antigen-presenting cells within 30 min after injection. The exogenous autoantigen dramatically changed the motility and function of autoreactive effector T cells within the EAE lesions: T cells that had been cruising through the tissue slowed down and became tethered to local antigen-presenting cells within 1 h. One hour later, the effector T cells massively produced proinflammatory cytokines and up-regulated membranous activation markers. This strong activation of the T cells boosted CNS inflammation and aggravated clinical disease. Postactivated effector and resting memory T cells specific for a non-CNS antigen (ovalbumin) were recruited to EAE lesions and moved there without contacting antigen-presenting cells. These cells were similarly arrested and activated after i.v. infusion of ovalbumin, and they also exacerbated clinical disease. Our data are relevant for autoantigen-based therapies of autoimmune disorders. Further, the study indicates how brain unrelated antigens (microbial components) leaking into the chronically inflamed CNS through the bloodstream might trigger relapses in multiple sclerosis.

| S-EPMC2141827 | biostudies-literature

STAT6 signaling pathway controls germinal center responses promoted after antigen targeting to conventional type 2 dendritic cells.

Project description:Conventional dendritic cells (cDCs) are antigen-presenting cells specialized in naïve T cell priming. Mice splenic cDCs are classified as cDC1s and cDC2s, and their main functions have been elucidated in the last decade. While cDC1s are specialized in priming type 1 helper T cells (TH1) and in cross presentation, cDC2s prime T follicular helper (TFH) cells that stimulate germinal center (GC) formation, plasma cell differentiation and antibody production. However, less is known about the molecular mechanisms used by cDCs to prime those responses. Here, using WT and STAT6-deficient mice (STAT6 KO), we targeted a model antigen to cDC1s and cDC2s via DEC205 and DCIR2 receptors, respectively, in an attempt to study whether the STAT6 signaling pathway would modulate cDCs' ability to prime helper T cells. We show that the differentiation and maturation of cDCs, after stimulation with an adjuvant, were comparable between WT and STAT6 KO mice. Besides, our results indicate that, in STAT6 KO mice, antigen targeting to cDC2s induced reduced TFH and GC responses, but did not alter plasma cells numbers and antibody titers. Thus, we conclude that the STAT6 signaling pathway modulates the immune response after antigen targeting to cDC2s via the DCIR2 receptor: while STAT6 stimulates the development of TFH cells and GC formation, plasma cell differentiation occurs in a STAT6 independent manner.

| S-EPMC9040147 | biostudies-literature

Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine.

Project description:Dendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b(+) DC subset, Notch signaling blockade ablated a distinct population marked by high expression of the adhesion molecule Esam. The Notch-dependent Esam(hi) DC subset required lymphotoxin beta receptor signaling, proliferated in situ, and facilitated CD4(+) T cell priming. The Notch-independent Esam(lo) DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b(+)CD103(+) DCs in the intestinal lamina propria and to a corresponding decrease of IL-17-producing CD4(+) T cells in the intestine. Thus, Notch2 is a common differentiation signal for T cell-priming CD11b(+) DC subsets in the spleen and intestine.

| S-EPMC3225703 | biostudies-literature

Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen.

Project description:Signaling through Notch receptors and their transcriptional effector RBP-J is essential for lymphocyte development and function, whereas its role in other immune cell types is unclear. We tested the function of the canonical Notch-RBP-J pathway in dendritic cell (DC) development and maintenance in vivo. Genetic inactivation of RBP-J in the bone marrow did not preclude DC lineage commitment but caused the reduction of splenic DC fraction. The inactivation of RBP-J in DCs using a novel DC-specific deleter strain caused selective loss of the splenic CD8(-) DC subset and reduced the frequency of cytokine-secreting CD8(-) DCs after challenge with Toll-like receptor ligands. In contrast, other splenic DC subsets and DCs in the lymph nodes and tissues were unaffected. The RBP-J-deficient splenic CD8(-) DCs were depleted at the postprogenitor stage, exhibited increased apoptosis, and lost the expression of the Notch target gene Deltex1. In the spleen, CD8(-) DCs were found adjacent to cells expressing the Notch ligand Delta-like 1 in the marginal zone (MZ). Thus, canonical Notch-RBP-J signaling controls the maintenance of CD8(-) DCs in the splenic MZ, revealing an unexpected role of the Notch pathway in the innate immune system.

| S-EPMC2118632 | biostudies-literature

The microRNA miR-155 controls CD8(+) T cell responses by regulating interferon signaling.

Project description:We found upregulation of expression of the microRNA miR-155 in primary effector and effector memory CD8(+) T cells, but low miR-155 expression in naive and central memory cells. Antiviral CD8(+) T cell responses and viral clearance were impaired in miR-155-deficient mice, and this defect was intrinsic to CD8(+) T cells, as miR-155-deficient CD8(+) T cells mounted greatly diminished primary and memory responses. Conversely, miR-155 overexpression augmented antiviral CD8(+) T cell responses in vivo. Gene-expression profiling showed that miR-155-deficient CD8(+) T cells had enhanced type I interferon signaling and were more susceptible to interferon's antiproliferative effect. Inhibition of the type I interferon-associated transcription factors STAT1 or IRF7 resulted in enhanced responses of miR-155-deficient CD8(+) T cells in vivo. We have thus identified a previously unknown role for miR-155 in regulating responsiveness to interferon and CD8(+) T cell responses to pathogens in vivo.

| S-EPMC3664306 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data