bluuebunny/crossref_metadata_2025_split huggingface dataset:
A predominance of M2b macrophages in mesenteric lymph nodes of mice exposed to whole body 137Cs γ-irradiation (89.32)
Authors: Kobayashi Makiko , Cornforth Michael , Kinoshita Manabu , Shinomiya Nariyoshi , Suzuki Fujio 
Published: January 2023

Abstract
In accompanying studies, we have demonstrated that mice exposed to 5 Gy whole body 137Cs γ-irradiation (5 GY-mice) are greatly susceptible to bacterial translocation. M1Mϕ (IL-12+IL-10− Mϕ), host defense effector cells against bacterial translocation, were not demonstrated in mesenteric lymph nodes (MLN) of these mice. M2Mϕ (IL-12−IL-10+ Mϕ) were predominated in MLN of 5 GY-mice. M2Mϕ are inhibitory on Mϕ conversion from resident Mϕ to M1Mϕ. In this study, MLN-M2Mϕ isolated from mice 14 days after 5 Gy γ-irradiation were characterized biophysically. F4/80+ cells (1 x 106 cells/ml) isolated from MLN were cultured with 106 heat-killed Enterococcus faecalis for 48 hrs. Culture fluids harvested were assayed for IL-10, CCL17, CCL1 and CXCL13 by ELISA. Also, cells harvested from the cultures were assayed for mannose receptor and LIGHT mRNA expression by RT-PCR. In the results, CCL1 and IL-10 were detected in the culture fluids of MLN F4/80+ cells isolated from 5 GY-mice. Also, these Mϕ expressed LIGHT mRNA. CCL17 and CXCL13 were not produced and mannose receptor mRNA was not expressed by these Mϕ. An 86% of antigen-stimulated Mϕ conversion from resident Mϕ to M1Mϕ was inhibited by MLN F4/80+ cells isolated from 5 GY-mice. CCL17 and mannose receptor are biomarkers of M2aMϕ, CCL1 and LIGHT are biomarkers of M2bMϕ, and CXCL13 and mannose receptor are biomarkers of M2cMϕ. These results indicate that F4/80+ Mϕ isolated from MLN of 5 GY-mice are M2bMϕ.
M1 macrophages as a major host defense effector cell in bacterial translocation induced by whole body 137Cs γ-irradiation (89.34)
Authors: Suzuki Fujio , Kinoshita Manabu , Shinomiya Nariyoshi , Cornforth Michael , Kobayashi Makiko 
Published: January 2023

Abstract
In thermally injured hosts, mesenteric lymph node macrophages (MLNMϕ) are identified as major effector cells against bacterial translocation. In this study, the antibacterial function of MLNMϕ from mice exposed to whole body γ-irradiation was investigated. BALB/c mice, 14 days after 0.5 (0.5 GY-mice) or 5 Gy (5 GY-mice) whole body γ-irradiation, were tested for their resistance against oral infection with 106 CFU/mouse of Enterococcus faecalis. Also, the resistance of decontaminated NOD-SCID IL-2rγ-/- mice (NOD-SCID mice), inoculated with MLNMϕ from 0.5 GY-mice or 5 GY-mice, to E. faecalis oral infection was examined. Furthermore, MLNMϕ isolated from 0.5 GY-mice and 5 GY-mice were biophysically characterized. In the results, 100% of 5 GY-mice died after E. faecalis oral infection, while 0.5 GY-mice similarly infected with the pathogen were shown to be resistant. All NOD-SCID mice inoculated with 5 GY-mouse MLNMϕ died after the infection, while 100% of these mice inoculated with 0.5 GY-mouse MLNMϕ survived. MLNMϕ from 0.5 GY-mice produced IL-12 (but not IL-10) and expressed iNOS mRNA. MLNMϕ from 5 GY-mice produced IL-10 (but not IL-12) and did not express iNOS mRNA. These results indicate that 0.5 GY-mouse MLNMϕ are M1Mϕ, and 5 GY-mouse MLNMϕ are M2Mϕ. Bacterial translocation in whole body γ-irradiated mice may be controlled by immunological intervention of M1Mϕ distributed in mesenteric lymph nodes.
Role of microRNA-214-targeting PTEN in advanced glycation endproducts-induced apoptosis delay of monocytes (89.35)
Authors: Zen Ke , Li Li-Min , Liu Dan-Qing , Guo Ya-Lan , Liu Yuan , Zhang Chen-Yu 
Published: January 2023

Abstract
Advanced glycation endproduct(AGE) delays spontaneous apoptosis of human monocytes and contributes to the development of a local inflammatory response. The mechanism by which AGEs effect monocyte apoptosis, however, is unclear. Here we report that AGE-modified BSA and β2-microglobulin(β2m) can increase miR-214 expression in monocytes, which in turn, enhances cell survival by reducing the expression of phosphatase and tensin homolog(PTEN). Employing miRNA microarray, we obtains a genome-wide miRNA expression profiling of THP-1 cells treated with/without AGEs. Among 470 miRNAs screened, 6 miRNAs including miR-214 are upregulated while 5 miRNAs were down-regulated (fold-change&gt;2) in AGE-treated cells. AGE-induced miRNA differential expression is validated by miRNA qRT-PCR. Significant upregulation of miR-214 is confirmed in normal human monocytes treated with AGEs and monocytes isolated from patients with chronic renal failure. Both AGE-treated monocytes and patient monocytes have a delayed apoptosis. Luciferase reporter assay shows that miR-214 targets PTEN mRNA 3’-untranslated region. Furthermore, PTEN expression is inversely correlated with miR-214 expression in monocytes and the forced expression of miR-214 leads to a delayed apoptosis of THP-1. In contrast, decrease of miR-214 expression via anti-miR-214 largely abolishes AGE-induced cell survival. In summary, our findings define a new regulation role of miR-214 on AGE-induced monocyte survival by impeding PTEN expression.
Impairment of human dendritic cell function by a food-borne carcinogenic heterocyclic aromatic amine, 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (89.38)
Authors: Kim SunKyung , Jeon Jun Ho , Im Jintaek , Yun Cheol-Heui , Han Seung Hyun 
Published: January 2023

Abstract
Carcinogens frequently provoke immunosuppressive effects and thereby cancer cells are not easily removed by host immune system having carcinogen(s). Heterocyclic amines (HCA) such as 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), are dietary carcinogens that are abundantly produced by overcooking meat and fish. Here, we investigated the effect of HCA on the activation of dendritic cells (DCs) which play an important role in the initiation of immune responses. When human monocyte-derived DCs were stimulated with lipopolysaccharide (LPS), DCs became mature with an increase in the expression of co-stimulatory receptors such as CD80 and CD86, and MHC molecules but a decrease in the phagocytic capacity. However, Trp-P-1 but not PhIP or IQ alleviated all of these phenomena under the same condition. In addition, Trp-P-1 inhibited the production of cytokines, TNF-α and IL-12, by LPS-stimulated DCs. Furthermore, DCs pre-exposed to Trp-P-1 were less efficient in the activation and proliferation of autologous T cells than the control DCs. The suppressive effect of Trp-P-1 on the LPS-induced DC activation appears to be due to interference with the interaction between LPS and DCs as determined by a binding assay using FITC-labeled LPS. Conclusively, these results suggest that Trp-P-1 impairs the function of DCs for the appropriate induction of immune responses.
Natural antibodies recognize cytoplasmic myosin that is cleaved and transferred to the cell membrane during apoptosis (89.4)
Authors: Cui Xiaoxuan , Zhang Lu , Magli Amanda , Catera Rosa , Kolitz Jonathan , Allen Steven , Rai Kanti , Chiorazzi Nicholas , Chu Charles 
Published: January 2023

Abstract
Natural antibodies (Abs) and Abs from patients with chronic lymphocytic leukemia (CLL) bind a subset of apoptotic cells that expose intracellular myosin on their surface. To test the mechanisms that produce myosin exposed apoptotic cells (MEACs), Jurkat T cells were induced to undergo intrinsic (spontaneous or camptothecin-induced) or extrinsic (Fas ligand- or anti-Fas-induced) apoptosis. After prolonged incubation by all methods, a high percentage of apoptotic cells became MEACs. Thus, both intrinsic and extrinsic apoptotic pathways lead to MEAC formation, suggesting that a common downstream mediator is involved. Consistent with this, a caspase-3 inhibitor reduced both apoptosis and MEAC formation, whereas a caspase-1 inhibitor had no effect. To test if caspase-3 cleavage resulted in membrane exposure of myosin, cytoplasmic and membrane protein extracts were examined for caspase-3 cleaved myosin fragments. MEAC extracts predominantly exhibited the expected 149 and 94 kDa myosin fragments in the membrane fraction. In contrast, live cell extracts exhibited predominantly the full-length myosin protein in the cytoplasmic fraction. These results indicate that MEAC formation occurs during intrinsic and extrinsic apoptosis when caspase-3 is activated. Caspase-3 cleavage of myosin produces fragments that reside in the cell membrane, where they become available to react with CLL and natural Abs.
ANCA antigen proteinase 3 acts as a phagocytotic receptor of bacteria via PAR2 pathway in human neutrophils. (89.40)
Authors: Kim Yongchul , Choi Youngnim , Shin Ji Eun , Kim Young suk 
Published: January 2023

Abstract
The molecular mechanisms underlying the phagocytosis of bacteria by neutrophils are pooly understood. We previously reported the efficient uptake of Streptococcus sangunis by human neutrophils in the absence of opsonins. To characterize the phagocytosis receptor, protein lysates of neutrophils and HL-60 cells were subjected to affinity chromatography using epoxy beads immobilized with S. sangunis. Denaturing electrophoresis of the eluted proteins revealed several neutrophil-specific bands. One of these proteins was identified as proteinase 3 (PR3) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which was confirmed by western blotting. PR3 is a serine proteinase of the azurophil granules and also co-expressed with NB1, a glycosylphosphatidylinositol (GPI)-linked receptor, on the surface of neutrophils. Enzymatic cleavage of GPI anchors or blocking of PR3 significantly reduced the ability of neutrophils to phagocytose S. sangunis. Protease activity was required for phagocytosis, and S. sanguinis and protease-activated receptor 2 (PAR2) agonist induced calcium mobilization in a homologous desensitization manner, indicating the involvement of PAR 2 in phagocytosis. Finally, exposure to S. sanguinis preferentially activated RhoA to Rac1 and Cdc42, which was blocked by an intracellular calcium chelator. Collectively, our data show that PR3 acts as a phagocytotic receptor via PAR2 and the Rho family GTPases in neutrophils.
Modulation of human immune responses by ginseng extracts (89.56)
Authors: Madrenas Joaquin , Toth Judit , Hewson Gillian , Frodermann Vanessa , Chau Luan 
Published: January 2023

Abstract
Ginseng (GS) has been used as an herbal remedy for centuries but its immunomodulatory effects remain unclear. Here we report the effects of standardized North-American ginseng (Panax quinquefollius) extracts (ethanol, aqueous and polysaccharide extracts) on innate and adaptive immune responses of human peripheral blood mononuclear cells (PBMCs) of healthy volunteers. We found that endotoxin (LPS)-free GS by itself induced the production of pro-inflammatory cytokines (IL-1β, IL-6, TNFα) and of IL-10 by PBMCs in a dose-dependent manner. Of the three extracts of GS tested, the aqueous extract was the most potent. GS extracts did not inhibit but rather enhanced the pro-inflammatory response induced by LPS. However, the T cell IL-2 response to bacterial superantigens was down-regulated in the presence of GS. Next, we examined the signalling pathways involved in the immune response to GS. We found that the GS aqueous extract activated the MAPK (ERK1/2, p38), the PI3K/Akt, and the NFκB pathways. Inhibition of src kinases and PKC decreased GS-induced cytokine production whereas inhibition of PI3K selectively blocked IL-10 production. Based on these results, we conclude that GS, and in particular its aqueous extract, has modulatory properties on innate and adaptive immunity. This work should help to focus the search for compounds in these extracts with specific immunomodulatory activities.
Gamma delta T cell subpopulations defined by expression of distinct sets of the co-receptor WC1 genes. (89.6)
Authors: Baldwin Cynthia , Chen Chuang 
Published: January 2023

Abstract
Gamma delta T cells can be 60% of peripheral blood mononuclear cells in young ruminants with the majority expressing the WC1 co-receptor. WC1 co-receptors are composed of up to eleven extracellular scavenger receptor (SRCR) domains with the interdomain pattern organized as a-[b-c-d-e-d’]-[b-c-d-e-d’] and the greatest differences occurring in the most distal domain 1 (‘a’ in the pattern). Two main subpopulations are defined by the presence of either the WC1.1 or the WC1.2-antigenic epitopes and these are functionally distinct since only a small subpopulation of WC1.1+ cells proliferate to antigens of Leptospira and produce IFN-γ in response to leptospira or IL-12. Prior to the onset of the studies described here the copy number of WC1 genes and the WC1 forms that account for the serologically-defined WC1.1 and WC1.2 were unknown. By applying real-time QPCR and relative quantification analysis, 13 WC1 domain 1 genes were found to be present in cattle from two breeds. In addition, we found 6 subpopulations of WC1+ γδ T cells defined by anti-WC1 subpopulation-specific mAbs and showed that this correlated with expression of different sets of WC1 genes. The studies described here demonstrate that more than one WC1 gene is expressed on a single WC1+ γδ T cells, that specific WC1 genes are associated with γδ T cell subpopulations defined by a panel of anti-WC1 subpopulation-specific mAbs and that these differences are likely to influence their response to various stimuli.
Intestinal ischemia/reperfusion-induced lipid alterations do not correlated with damage or PGE2 production (90.12)
Authors: Archer Slone Emily , Sparkes Byron , Roth Mary , Welti Ruth , Fleming Sherry 
Published: January 2023

Abstract
Ischemia/reperfusion (IR)-induced injury results in severe tissue damage and causes up to 30,000 human deaths per year in the US. In a mouse model of intestinal IR, C57Bl/6 mice experience significant intestinal damage; however Rag-1-/- mice, which are antibody deficient, do not sustain significant damage. Complement activation is also critical as indicated by the lack of damage in complement receptor 2 deficient (CR2-/-) mice. Additionally, when Rag-1-/- or CR2-/- mice are pretreated with C57Bl/6 antibodies or specific anti-phospholipid monoclonal antibodies, damage is restored to C57Bl/6 levels. We hypothesized that antibodies recognize a specific lipid antigen produced during IR. After subjecting C57Bl/6, CR2-/- and Rag-1-/- mice to either Sham or intestinal ischemia followed by reperfusion, we determined jejunal prostaglandin E2 (PGE2) production and lipid profile. Mass spectrometry analysis of extracted lipids indicated that lysolipids and arachidonic acid (AA) levels increased by 15 min post-ischemia in C57Bl/6 mice. Differences in lysolipids or AA will be detected between C57Bl/6, CR2-/- and Rag-1-/- mice. C57Bl/6 mice produced significantly more Cox-2 mRNA and PGE2 than either CR2-/- or Rag-1-/- mice. Pretreating Rag-1-/- mice with antibodies purified from C57Bl/6 mice restored IR-induced PGE2 production to C57Bl/6 levels. We conclude that antibodies do not influence lipid metabolism, but are required for activation of Cox-2 and subsequent production of PGE2.
Induction of Th17 responses during vaccination: influence of route of immunization. (90.16)
Authors: Norton Elizabeth , Louise Lawson , Clements John , Cardenas-Freytag Lucia 
Published: January 2023

Abstract
The role of Th17 cells in vaccine-induced immune responses is poorly understood. A growing body of evidence suggests that some adjuvants, such as cholera toxin from Vibrio cholerae and heat-labile toxin (LT) from Escherichia coli, can promote development of Th17 responses. We investigated the presence of Th17 cells after immunization with tetanus toxoid (TT) with and without the inclusion of a detoxified form of LT designated LT(R192G/L211A), or dmLT. Groups of BALB/c mice were immunized twice (day 0, 30) with TT alone or in conjunction with dmLT either mucosally (oral, intranasal, intrarectal) or parentally (subcutaneous). Animals were sacrificed 30 days after the last immunization and splenocytes were harvested for in vitro restimulation assays. Recipients of TT + dmLT by all mucosal routes had elevated levels of TT-specific Th17 cells compared to groups immunized parenterally or with TT alone by any route. Intranasal immunization with TT + dmLT induced particularly strong Th17 responses, with significant levels of IL-17 detected in antigen-restimulated splenocyte supernatants. Collectively, these results suggest that mucosal immunization in the presence of an appropriate immunostimulant, such as the adjuvant dmLT, can direct the development of Th17 responses. The observation that antien-specific Th17 cells were only detected following mucosal immunization suggests that Th17 responses may play a critical role in mucosal immune responses and mucosal vaccine-based protection.
Essential role of membrane trafficking factor AP-1B in gut immune homeostasis (90.4)
Authors: Takahashi Daisuke , Hase Koji , Kimura Shunsuke , Ohno Hiroshi 
Published: January 2023

Abstract
Intestinal epithelium covering the mucosal surface play an important role to maintain homeostatic balance between immunity and tolerance in the gut; however, the molecular mechanisms that control this function of intestinal epithelium remains to be elucidated. Epithelium-specific adaptor protein (AP) complex AP-1B, contributes to basolateral sorting of certain membrane proteins, which is essential for polarity formation and maintenance. We found that mice deficient in AP-1B caused severe chronic inflammation in the colon, characterized by crypt elongation, decrease in goblet cells, massive infiltration of CD11b+ dendritic cells (DCs) and TH17 cells. CD11b+ DCs prepared from the colon of AP-1B-deficient mice produced high amounts of IL-1β and TNF-α no matter if stimulated with LPS or not, whereas those from control mice did not release detectable amount of these cytokines even upon stimulation with LPS, suggesting a defect in immunological tolerance in AP-1B-deficient mice. This could be due to abrogated epithelial innate immune function, because reduced expression of antimicrobial proteins by colonic epithelium and bacterial penetration into the lamina propria were evident in AP-1B-deficient mice. Our data clearly suggest that appropriate protein sorting by AP-1B is necessary for formation and/or maintenance of epithelial integrity that is important for containment of excessive inflammatory response in the colon.
Type I interferon reverses human Th2 commitment and stability by repressing GATA3 (91.11)
Authors: Huber Jonathan , Ramos Hilario , Gill Michelle , Farrar J. 
Published: January 2023

Abstract
CD4+ T helper-type 2 (Th2) cells regulate inflammatory responses to helminth infections while also mediating pathological processes of asthma and allergy. IL-4 drives Th2 development by inducing the expression of the GATA3 transcription factor. GATA3 positively reinforces its own expression thereby promoting IL-4-independent stability in Th2 cells. In this study, we found that type I interferon (IFN-α/β) potently blocked human Th2 development and inhibited cytokine secretion from pre-committed Th2 cells. Further, IFN-α/β inhibited Th2 cytokine secretion from CRTH2+ cells isolated from peripheral blood. This negative regulatory pathway was operative in human, but not mouse CD4+ T cells and was specific to type I interferon as neither IL-12 nor IFN-γ mediated such inhibition. IFN-α/β blocked Th2 cytokine secretion through the inhibition of GATA3 expression during both Th2 development and in fully committed Th2 cells. Thus, we demonstrate a novel role for IFN-α/β in blocking Th2 commitment, highlighting its potential as a therapy for atopy and asthma.
Airway epithelium response to IFN-γ regulates allergic airway inflammation (91.7)
Authors: Mitchell Charlotte , Provost Karin , Niu Naiqian , Homer Robert , Cohn Lauren 
Published: January 2023

Abstract
IFN-γ produced by Th1 cells inhibits Th2-induced allergic airway disease by decreasing airway eosinophilia, mucus production and chitinase activity. To define pathways by which IFN-γ inhibits allergic airway inflammation, we generated bone marrow chimeras with IFN-γ receptor (IFN-γR) deficient mice, transferred OVA-specific Th1, Th2 or Th1+Th2 cells and exposed mice to inhaled OVA. In mice receiving Th1+Th2 cells, IFN-γR was required on both hematopoietic and non-hematopoietic cells for maximal inhibition of mucus and chitinase activity, while IFN-γR expression on hematopoietic cells was sufficient for inhibition of airway eosinophilia. We hypothesized that airway epithelial cells are essential non-hematopoietic cells required to mediate the inhibitory effects of IFN-γ during airway inflammation. We generated epi-IFN-γR mice that express IFN-γR only on airway epithelial cells. Epi-IFN-γR mice that received Th1+Th2 cells showed near total inhibition of mucus, suggesting that IFN-γ directly inhibits mucus in epithelial cells. In epi-IFN-γR mice that received Th1+Th2 cells there was partial inhibition of chitinase activity, likely due to direct effects of IFN-γ on the epithelium. In epi-IFN-γR mice, airway eosinophilia was moderately inhibited through effects on eosinophil development in the bone marrow. These studies show the importance of airway epithelial cells in the regulation of allergic airway disease and highlight the epithelium as a target for therapy in airway disease.
Glutamate signaling through the kainate receptor is critical for human B cell IgE production (91.9)
Authors: Sturgill Jamie , Conrad Daniel 
Published: January 2023

Abstract
Glutamate, the major excitatory neurotransmitter, has recently been implicated in a variety of diseases. Patients with HIV, certain cancers, and autoimmune illnesses have elevated levels of glutamate in the periphery. While glutamate receptor signaling has been examined in T cells, there are currently no published observations on the effects of glutamatergic stimuli on B cells. Human B cells were first examined for the presence of glutamate receptors via RT-PCR and Western Blot. The kainate receptor (KAR), a specific subtype of ionotropic glutamate receptor was found on human B cells. We found that KAR activation increased ADAM10 mRNA which is in agreement with receptor activity in the CNS. A significant corresponding increase in CD23 released into the supernatant was seen as ADAM10 has been identified as the protease responsible for CD23’s ectodomain shedding. Remarkably, we also detect a strong increase in cellular proliferation and IgE synthesis. Thus, we report for the first time the unique presence of a neurotransmitter receptor and that activation of this receptor could serve as a novel mechanism for enhancing B cell activation. This enhancement has implications for allergic and autoimmune diseases.