scholarly journals LY6S, a New Interferon-Inducible Human Member of the Ly6a-Subfamily Expressed by Spleen Cells and Associated with Inflammation and Viral Resistance

2021 ◽  
Author(s):  
Moriya Shmerling ◽  
Michael Chalik ◽  
Nechama I Smorodinsky ◽  
Alan Meeker ◽  
Sujayita Roy ◽  
...  
Keyword(s):  
Immune Responses ◽  
Gene Cluster ◽  
Cell Lineage ◽  
Chromosome 8 ◽  
Viral Resistance ◽  
Human Interferon ◽  
Chromosome 15 ◽  
Spleen Cells ◽  
Inflammatory Phenotype ◽  
Resistance To Viral Infection

Syntenic genomic loci on human chromosome 8 (hChr8) and mouse chromosome 15 (mChr15) code for LY6/Ly6 (lymphocyte antigen 6) family proteins. The 23 murine Ly6 family genes include eight genes that are flanked by the murine Ly6e and Ly6l genes and form an Ly6 subgroup referred to here as the Ly6a subfamily gene cluster. Ly6a, also known as Sca1 (Stem Cell Antigen-1) and TAP (T-cell activating protein), is a member of the Ly6a subfamily gene cluster. No LY6 genes have been annotated within the syntenic LY6E to LY6L human locus. We report here on LY6S, a solitary human LY6 gene that is syntenic with the murine Ly6a subfamily gene cluster, and with which it shares a common ancestry. LY6S codes for the interferon-inducible GPI-linked LY6S-iso1 protein that contains only 9 of the 10 consensus LY6 cysteine residues and is most highly expressed in a non-classical cell population. Its expression leads to distinct shifts in patterns of gene expression, particularly of genes coding for inflammatory and immune response proteins, and LY6S-iso1 expressing cells show increased resistance to viral infection. Our findings reveal the presence of a previously un-annotated human interferon-stimulated gene, LY6S, which has a one to eight ortholog relationship with the genes of the Ly6a subfamily gene cluster, is most highly expressed in spleen cells of a non-classical cell-lineage and whose expression induces viral resistance and is associated with an inflammatory phenotype and with the activation of genes that regulate immune responses.

Nicotinic receptor gene cluster on rat chromosome 8 in nociceptive and blood pressure hyperresponsiveness

2002 ◽  
Vol 11 (2) ◽  
pp. 65-72 ◽  
Author(s):  
Imran M. Khan ◽  
Erin Singletary ◽  
Adamu Alemayehu ◽  
Shanaka Stanislaus ◽  
Morton P. Printz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Gene Cluster ◽  
Nicotinic Receptor ◽  
Receptor Gene ◽  
Repeated Administration ◽  
Chromosome 8 ◽  
Brown Norway ◽  
Spontaneously Hypertensive ◽  
Nicotinic Agonists ◽  
Nociceptive Responses

Spontaneously hypertensive rats (SHR) exhibit enhanced pressor, heart rate, and nociceptive responses to spinal nicotinic agonists. This accompanies a paradoxical decrease in spinal nicotinic receptor number in SHR compared with normotensive rats. The congenic strain, SHR-Lx, with an introgressed chromosome 8 segment from the normotensive Brown-Norway-Lx strain (BN-Lx) exhibits reduced blood pressure. This segment contains a gene cluster for three nicotinic receptor subunits expressed in the nervous system. We examined the implication of this gene cluster in the enhanced responsiveness of the SHR. Pressor and nociceptive responses to spinal cytisine, a nicotinic agonist, were diminished in SHR-Lx. Moreover, with repeated administration, these responses desensitized faster in SHR-Lx and progenitor BN-Lx than in progenitor SHR/Ola. This implicates the gene cluster in both cardiovascular and nociceptive responses to spinal nicotinic agonists. Since diminished responsiveness to agonist stimulation is greater than the basal blood pressure differences between the strains and the introgressed rat chromosome maps to a quantitative trait locus in human hypertension, polymorphisms in the three nicotinic receptor genes become candidates for altered central control of blood pressure.

scholarly journals Multiparameter Flow Cytometry Analysis of the Human Spleen Applied to Studies of Plasma-Derived EVs From Plasmodium vivax Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Melisa Gualdrón-López ◽  
Míriam Díaz-Varela ◽  
Haruka Toda ◽  
Iris Aparici-Herraiz ◽  
Laura Pedró-Cos ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Responses ◽  
Plasmodium Vivax ◽  
Size Exclusion ◽  
Multiparameter Flow Cytometry ◽  
Spleen Cells ◽  
Human Spleen ◽  
Hematopoietic Stem ◽  
Ethical Implications ◽  
Cellular Analysis

The spleen is a secondary lymphoid organ with multiple functions including the removal of senescent red blood cells and the coordination of immune responses against blood-borne pathogens, such as malaria parasites. Despite the major role of the spleen, the study of its function in humans is limited by ethical implications to access human tissues. Here, we employed multiparameter flow cytometry combined with cell purification techniques to determine human spleen cell populations from transplantation donors. Spleen immuno-phenotyping showed that CD45+ cells included B (30%), CD4+ T (16%), CD8+ T (10%), NK (6%) and NKT (2%) lymphocytes. Myeloid cells comprised neutrophils (16%), monocytes (2%) and DCs (0.3%). Erythrocytes represented 70%, reticulocytes 0.7% and hematopoietic stem cells 0.02%. Extracellular vesicles (EVs) are membrane-bound nanoparticles involved in intercellular communication and secreted by almost all cell types. EVs play several roles in malaria that range from modulation of immune responses to vascular alterations. To investigate interactions of plasma-derived EVs from Plasmodium vivax infected patients (PvEVs) with human spleen cells, we used size-exclusion chromatography (SEC) to separate EVs from the bulk of soluble plasma proteins and stained isolated EVs with fluorescent lipophilic dyes. The integrated cellular analysis of the human spleen and the methodology employed here allowed in vitro interaction studies of human spleen cells and EVs that showed an increased proportion of T cells (CD4+ 3 fold and CD8+ 4 fold), monocytes (1.51 fold), B cells (2.3 fold) and erythrocytes (3 fold) interacting with PvEVs as compared to plasma-derived EVs from healthy volunteers (hEVs). Future functional studies of these interactions can contribute to unveil pathophysiological processes involving the spleen in vivax malaria.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (3) ◽  
pp. 648-659 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Stuart Schlossman ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Suppressor Cells ◽  
Specific Response ◽  
Spleen Cells ◽  
X Irradiation

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-θ serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained θ-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.

scholarly journals Effects of dietary oxidized frying oil on immune responses of spleen cells in rats

1997 ◽  
Vol 17 (4) ◽  
pp. 729-740 ◽  
Author(s):  
Bi-Fong Lin ◽  
Ying-Jung Wu ◽  
Bor-Luen Chiang ◽  
Jen-Fang Liu ◽  
Ching-Jang Huang
Keyword(s):  
Immune Responses ◽  
Frying Oil ◽  
Spleen Cells

scholarly journals Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation.

1990 ◽  
Vol 171 (1) ◽  
pp. 265-292 ◽  
Author(s):  
M Shlomchik ◽  
M Mascelli ◽  
H Shan ◽  
M Z Radic ◽  
D Pisetsky ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cell Activation ◽  
Specific Antigen ◽  
B Cell Activation ◽  
Spleen Cells ◽  
Systemic Autoimmune Diseases ◽  
Proximate Cause ◽  
Arginine Residues ◽  
Dna Antibodies

The proximate cause of autoantibodies characteristic of systemic autoimmune diseases has been controversial. One hypothesis is that autoantibodies are the result of polyclonal nonspecific B cell activation. Alternatively, autoantibodies could be the result of antigen-driven B cell activation, as observed in secondary immune responses. We have approached this question by studying monoclonal anti-DNA autoantibodies derived from unmanipulated spleen cells of the autoimmune MRL/lpr mouse strain. This analysis shows that anti-DNAs, like rheumatoid factors (19), are the result of specific antigen-driven stimulation. In addition, correlation of sequences with fine specificity shows that: (a) somatic mutations can cause specificity for dsDNA and that such mutations are selected for; (b) arginine residues play an important role in determining specificity; and (c) anti-idiotypes that recognize the majority of anti-DNA are probably not specific for any one family of V regions.

scholarly journals Circulating Levels of Osteopontin in Patients With Psoriasis: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 4 (1) ◽  
pp. 15-21
Author(s):  
Aikaterini Kyriakou ◽  
Aikaterini Patsatsi ◽  
Nikiforos Galanis ◽  
Dimitrios G. Goulis
Keyword(s):  
Immune Responses ◽  
Meta Analysis ◽  
Cell Lineage ◽  
Severity Index ◽  
Random Effects Model ◽  
Study Quality ◽  
Psoriasis Area Severity Index ◽  
Pubmed Central ◽  
Meta Regression Analysis ◽  
Circulating Levels

Background: Both Th1 and Th17 have been proposed to be pathogenically essential in psoriasis. Osteopontin (OPN) is known to enhance Th1 responses, inhibit Th2 ones, and take part in the modulation of Th17 cell lineage. Due to its impact on Th1/Th17 immune responses, several reports have suggested that OPN may be of pathogenic importance in psoriasis. Our objective was to review the literature for studies that have assessed the circulating levels of OPN in psoriatic cases and controls and to meta-analyze the evidence obtainable. Methods: Search was performed in PubMed, Central, and Embase. Eligible were studies that have assessed OPN concentrations in patients with psoriasis and a group of reference. Results: Patients with psoriasis had increased OPN concentrations compared with controls (random-effects model, standardized mean difference: 1.58 ng/mL, 95% confidence interval: 0.90-2.26; P < .0001]). Heterogeneity among studies was high ( I2: 92.2%; P < .0001). The meta-regression analysis showed that the study quality (RTI score) reduced heterogeneity ( I2: 85.2%; P < .005), but not age, body mass index (BMI), Psoriasis Area Severity Index, or matching for BMI. Conclusions: This meta-analysis provided evidence that OPN is involved in the pathogenesis of psoriasis, enlarging the list of cytokines able to stimulate the inflammatory response in this disease.

scholarly journals Bartonella henselae-Specific Cell-Mediated Immune Responses Display a Predominantly Th1 Phenotype in Experimentally Infected C57BL/6 Mice

2001 ◽  
Vol 69 (10) ◽  
pp. 6427-6433 ◽  
Author(s):  
Mardjan Arvand ◽  
Ralf Ignatius ◽  
Thomas Regnath ◽  
Helmut Hahn ◽  
Martin E. A. Mielke
Keyword(s):  
Immune Responses ◽  
Bartonella Henselae ◽  
Interleukin 4 ◽  
Infection Model ◽  
Antibody Concentration ◽  
Specific Cell ◽  
Spleen Cells ◽  
Viable Bacteria ◽  
Igg Isotypes

ABSTRACT Immune responses of the immunocompetent host to Bartonella henselae infection were investigated in the murine infection model using C57BL/6 mice. Following intraperitoneal infection with human-derived B. henselae strain Berlin-1, viable bacteria could be recovered from livers and spleens during the first week postinfection, while Bartonella DNA remained detectable by PCR in the liver for up to 12 weeks after infection. Granulomatous lesions developed in livers of infected mice, reached maximal density at 12 weeks after infection, and persisted for up to 20 weeks, indicating that B. henselae induced a chronic granulomatous hepatitis in the immunocompetent murine host. T-cell-mediated immune responses were analyzed in vitro by means of spleen cell proliferation and cytokine release assays as well as analysis of immunoglobulin G (IgG) isotypes. Spleen cells from infected mice proliferated specifically upon stimulation with heat-killedBartonella antigen. Proliferative responses were mainly mediated by CD4+ T cells, increased during the course of infection, peaked at 8 weeks postinfection, and decreased thereafter. Gamma interferon, but not interleukin-4, was produced in vitro by spleen cells from infected animals upon stimulation withBartonella antigens. Bartonella-specific IgG was detectable in serum of infected mice by 2 weeks, and the antibody concentration peaked at 12 weeks postinfection. IgG2b was the prominent isotype among the Bartonella-specific serum IgG antibodies. These data indicate that B. henselaeinduces cell-mediated immune responses with a Th1 phenotype in immunocompetent C57BL/6 mice.

Donor-Specific Tolerance Induction through Expansion of DCregs and Tregs by a Liposomal Formulation of KRN7000 (RGI-2001).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2332-2332
Author(s):  
Omar Duramad ◽  
Amy Laysang ◽  
Jun Li ◽  
Yasuyuki Ishii ◽  
Reiko Namikawa
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Immune Responses ◽  
Treg Cells ◽  
Liposomal Formulation ◽  
Spleen Cells ◽  
Inkt Cells ◽  
Donor Specific Tolerance ◽  
Dose Dependent ◽  
Specific Tolerance

Abstract Pharmacological induction of donor-specific tolerance would provide significant benefits in both organ transplantation and bone marrow transplantation settings. We investigated the ability of alpha-galactosylceramide (α-GC) in inducing donor-specific tolerance when given in a liposomal formulation. α-GC is a ligand for CD1d molecules expressed on antigen-presenting cells. Upon presentation by CD1d to invariant natural killer T (iNKT) cells, α-GC induces the rapid release of Th1, Th2, or immune regulatory cytokines and initiation of multiple downstream cellular events such as T cell polarization and expansion of dendritic cell subsets. Previously, using RGI-2001 (a liposomal formulation of a synthetic derivative of α-GC, KRN7000), we have demonstrated that the activation of iNKT cells by RGI-2001 induces expansion of regulatory dendritic cells (DCreg) and subsequent generation of antigen-specific Foxp3+ regulatory T (Treg) cells in the presence of target antigens. In the present study, we examined the effects of RGI-2001 on immune responses against alloantigens using a murine in vivo experimental system. In brief, Balb/c (H-2d) recipients were primed with 5x10e6 C57BL/6 (H-2b) whole spleen cells (WSC) with varying doses of RGI-2001 (0.002 to 20 μg/mouse) given intravenously. Seven days later, WSC from the Balb/c recipients were examined for their cellular composition by FACS analysis. Subtle but reproducible dose-dependent increases were noted in the percentage of the LinnegCD11cintCD45RB+ dendritic cell (DC) population, known to be enriched for regulatory DC (DCreg). Since RGI-2001 induces an increase in the total spleen cells, the absolute DCreg cell numbers in RGI-2001-treated spleen increased in a statistically significant manner as compared with untreated controls. As for the percentages of CD4+Foxp3+ Treg cells, no apparent differences were observed. However, an analysis using the Ki67 cycling cell specific nuclear marker revealed a clear dose-dependent increase in the cycling cell fraction among CD4+Foxp3+ Treg cells. These results together confirmed that RGI-2001 induces expansion of DCregs and Tregs. Next, we investigated the effects of RGI-2001 on immune responses against the donor alloantigens. The WSC of the recipient mice were restimulated in vitro with the mitomycin C-treated, T cell depleted donor (C57BL/6) WSC, and the levels of proliferation were measured by MTT colorimetric assay (one-way MLR). It was found that RGI-2001 treatment reproducibly and significantly suppressed proliferation of host WSC in response to donor alloantigens. A dose of 2μg/mouse of RGI-2001 induced in average ~30% reduction in host WSC proliferation. IL-2 production was also reduced to ~50%, further indicating the suppressive effects of RGI-2001. Notably, it was confirmed that suppressive effect of RGI- 2001 was restricted to the responses towards donor specific alloantigens, as no suppression in proliferation nor IL-2 production was noted when a third party (C3H) WSC was used as the stimulators. Collectively, the results suggest that RGI-2001, when administered together with allogeneic donor cells, can induce donor specific tolerance by expanding DCregs and inducing antigen-specific Tregs. RGI-2001 may have a potential to be a novel therapy to prevent organ rejection as well as GvHD in bone marrow transplantation.

scholarly journals Laccases Involved in 1,8-Dihydroxynaphthalene Melanin Biosynthesis in Aspergillus fumigatus Are Regulated by Developmental Factors and Copper Homeostasis

2013 ◽  
Vol 12 (12) ◽  
pp. 1641-1652 ◽  
Author(s):  
Srijana Upadhyay ◽  
Guadalupe Torres ◽  
Xiaorong Lin
Keyword(s):  
Immune Responses ◽  
Aspergillus Fumigatus ◽  
Gene Cluster ◽  
Gene Expression Pattern ◽  
Copper Homeostasis ◽  
Copper Level ◽  
Fungal Virulence ◽  
Copper Transporter ◽  
Melanin Biosynthesis ◽  
Content Type

ABSTRACTAspergillus fumigatusproduces heavily melanized infectious conidia. The conidial melanin is associated with fungal virulence and resistance to various environmental stresses. This 1,8-dihydroxynaphthalene (DHN) melanin is synthesized by enzymes encoded in a gene cluster inA. fumigatus, including two laccases, Abr1 and Abr2. Although this gene cluster is not conserved in all aspergilli, laccases are critical for melanization in all species examined. Here we show that the expression ofA. fumigatuslaccases Abr1/2 is upregulated upon hyphal competency and drastically increased during conidiation. The Abr1 protein is localized at the surface of stalks and conidiophores, but not in young hyphae, consistent with the gene expression pattern and its predicted role. The induction of Abr1/2 upon hyphal competency is controlled by BrlA, the master regulator of conidiophore development, and is responsive to the copper level in the medium. We identified a developmentally regulated putative copper transporter, CtpA, and found that CtpA is critical for conidial melanization under copper-limiting conditions. Accordingly, disruption of CtpA enhanced the induction ofabr1andabr2, a response similar to that induced by copper starvation. Furthermore, nonpigmentedctpAΔ conidia elicited much stronger immune responses from the infected invertebrate hostGalleria mellonellathan the pigmentedctpAΔ or wild-type conidia. Such enhancement in elicitingGalleriaimmune responses was independent of thectpAΔ conidial viability, as previously observed for the DHN melanin mutants. Taken together, our findings indicate that both copper homeostasis and developmental regulators control melanin biosynthesis, which affects conidial surface properties that shape the interaction between this pathogen and its host.

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