bluuebunny/crossref_metadata_2025_split huggingface dataset:
From horses to high school - bringing Pigeon Fever studies into the classroom (37.3)
Authors: Haus Mary , Pollock Roberta 
Published: January 2023

Abstract
Pigeon Fever is an equine disease caused by Corynebacterium psuedotuberculosis. It manifests itself in three forms; external abscesses, internal abscesses, and ulcerative lymphangitis. The hypothesis is that the different manifestations of the disease are due to differences in TH1 versus TH2 responses in infected horses. ELISA tests were used to determine the antibody response to phospholipase D (PLD), the antigen produced by the bacteria. Current diagnostic tools state that horses with internal abscesses have high titers to PLD and horses with external abscesses have low titers. Our results show that while most horses with internal abscesses show high antibody responses to PLD, many horses with external abscesses and some uninfected horses also show high titers to PLD. Another possible tool for diagnosing and studying this disease is by typing monoclonal antibodies to determine the class and subclasses of anti-PLD antibodies being produced to test whether TH1 or TH2 induced antibodies predominate. These monoclonal antibodies have been made by R. Pollock and her colleagues and some have been typed; additional typing of these antibodies will be done by an Advanced Placement Biology class. In doing so, students will not only be able to learn about the immune response in the context of this disease, but actually contribute to an ongoing "real" research project.
Case Study That Focuses On Viral Replication That Enables Students To Understand How Easily Infection Is Transmitted (37.5)
Authors: Jarigese Kevin 
Published: January 2023

Abstract
Case Study That Focuses On Viral Replication That Enables Students To Understand How Easily Infection Is TransmittedKevin J. Jarigese, MST, Science Teacher, West Mesa High School, 6701 Fortuna Road NW, Albuquerque, NM 87121.
This case study is an educational unit developed for beginning biology students. In this unit, students will review an actual case study of a woman who works in a nursing home that is exposed to influenza virus. Through student group evaluations of behavioral issues, evaluation of the effects of vaccines on the epidemiology, and how infectious diseases may spread, students will develop a diagnosis and evaluate courses of action to be taken by patients and health care professionals. A focus on the issues of scientific literacy and the blending of concepts, history, and philosophy will be worked into the case study to help students evaluate and understand the scientific issues of our time.
Interactive computer simulations for teaching tumor immunology (37.8)
Authors: Dokken Nels , Habig Jeff , Otter Tim , Pennell Christopher A 
Published: January 2023

Abstract
We have created computer models to teach principles of cell biology, experimental design and data analysis associated with tumor immunology. The series of models presented here introduce two key concepts in tumor immunology. The first is that cancer arises from the accumulation of mutations, which results in uncontrolled proliferation and spread. The second concept is immune surveillance, which posits that in healthy individuals tumors are recognized and eliminated by the immune system before progressing to clinical disease. We illustrate both concepts by modeling interactions between tumor cells and immune effector cells. Students can study the effects of mutations on tumor cell survival and proliferation, and understand the mechanisms of immune evasion by monitoring gene expression and intracellular resources, and by analyzing metabolic regulatory networks that control emergent cell behaviors for each cell type or lineage. Because of their versatility, ease of use, Internet availability, and compatibility with readily available computing equipment, these models are well suited for a discovery-based learning approach as well as other teaching methods in secondary and college environments. More information about using simulations in education is available at http://www.cdres.com/education.
A predominant role for p75TNFR in TNF-induced CCL1 production (38.12)
Authors: Thomas Heather J , Lipsky Brian , Mozaffarian Afsi , Born Teresa 
Published: January 2023

Abstract
The proinflammatory activities of TNF are primarily mediated through p55TNFR, whereas little is known about the specific functions of p75TNFR. A preponderance of the literature, as well as our expression testing, suggests T cell populations uniquely tend to express more p75TNFR than p55TNFR protein, and the role of p75TNFR in murine thyomcyte development is well established. For these reasons, we studied the murine cytotoxic T cell line CT6 in search of novel consequences of p75TNFR engagement. These cells express high levels of p75TNFR and little p55TNFR. TLDA analysis showed upregulation of the chemokine CCL1/TCA-3 in response to TNF stimulation. ELISA experiments confirmed a striking TNF-induced secretion of CCL1 in these cells. CCL1 induction could be induced by agonistic p75TNFR-specific antibodies, and the TNF-induced response could be inhibited by p75TNFR blocking antibodies. Consistent with data in CT6 cells, CCL1 could be detected in the serum of animals, and serum levels increased 2-3 fold four hours following injection with TNF. This induction was maintained in p55TNFR knockout animals. Our data suggests that induction of the chemokine CCL1/TCA-3 in response to TNF stimulation is driven primarily by p75TNFR signaling. A better understanding of p75TNFR-dependent CCL1 induction will likely provide more insight into the protective or pathological role of p75TNFR in immune disease.
Defensins block the release but not the processing of IL-1beta and IL-18 from human monocytes (38.13)
Authors: Shi Jishu , Lan Liqiong , Aono Shelly , Morrison Edward , Lu Wuyuan 
Published: January 2023

Abstract
We have previously shown that human defensins can block the release of IL-1beta from LPS-primed human monocytes stimulated with ATP. The objective of this study is to determine whether defensins can inhibit the release IL-1beta and IL-18 from LPS-primed human monocytes stimulated with other inflammasome activators. LPS-activated (20 ng/ml, 2 h), 35S-methionine-labeled (1 h) human monocytes were treated with human defensin HD-5 in the presence or absence of ATP, monosodium urate (MSU), nigericin (Nig) for 90 min. Media and cell-associated fractions were harvested separately. IL-1beta was recovered from each by immunoprecipitation and caspase-1 was examined by western blot analysis. Mature IL-1beta and active caspase-1 were detected in the cytosol fraction from cells treated with HD-5. Thus, HD-5 blocked the release of mature IL-1beta from cells treated with ATP, MSU, or Nig. However, HD-5 did not inhibit ATP-, MSU-, or Nig-induced caspase-1 activation and processing of IL-1beta. In addition, HD-5 also blocked the release of IL-18 from LPS-primed human monocytes stimulated with ATP. To our knowledge, HD-5 is the first known endogenous inhibitor of IL-1beta and IL-18 release. These studies suggest that processing and release of IL-1beta are independent processes.
PGE2 affects the IL-12/IL-23 balance in mature myeloid dendritic cells (38.14)
Authors: Kocieda Virginia Polonia , Khayrullina Tanzilya , Ganea Doina 
Published: January 2023

Abstract
Following TLR signaling dendritic cells (DC) produce pro-inflammatory cytokines including IL-12 and IL-23. IL-12 promotes differentiation of the Th1 subset whereas IL-23 maintains the Th17 subset. PGE2, a lipid mediator, is produced by DC during inflammation. This study is focused on the effects of PGE2 on the regulation of IL-12/IL-23 production in murine DC. PGE2 inhibits LPS-induced IL-12 production through downregulation of p35, and stimulates IL-23 through upregulation of p19 expression. Changes in p35/p19 expression reduce Th1 and promote Th17 differentiation. Similar PGE2 effects on p19/p35 were observed in the presence of other TLR ligands, such as peptidoglycan (TLR2), poly I:C (TLR3) and CpG (TLR9). The effects of PGE2 on p19/p35 were mediated through EP2 and EP4 receptors, and cAMP induction. The involvement of downstream signaling pathways such as PKA and EPAC-induced activation of PI3K and GSK3, as well as the role of specific transcription factors such as CREB, cRel, and IRF5 (for p19 expression) and IRF 1, 3, 7, and RelA (for p35 expression) are currently being investigated.
Research support: NIH2RO1AI052306 & NSF Pre-doctoral Fellowship (VK)
Effects of interferon-a and interferon-b on development of antigen-specific B cells and hybridoma generation (38.28)
Authors: Santulli-Marotto Sandra , Petley Ted , Fisher Jamie , Pitcher Jennifer , Rycyzyn Michael , Giles-Komar Jill 
Published: January 2023

Abstract
The ratio of Interferon-α (IFN-α) and Interferon-β (IFN-β) produced during an immune response can significantly impact the outcome. We find that administration of IFN-α and IFN-β during immunization can alter the fate of antigen-specific B cells with minimum affect on antibody titers in mice. In vitro stimulation with IFN-α and IFN-β either individually or in combination triggered variations in interferon-responsive gene expression that directly correlated to the activity level of the individual interferons as well as the ratio of IFN-α to IFN-β. However, when the activity of IFN-α and IFN-β was normalized according to gene expression profiles the outcome of immunizing mice with the same antigen, using the same protocol but varying relative ratios of IFN-α and IFN-β yielded little to no antigen-specific B cells. Though animals could produce nearly identical antigen-specific antibody titers there was an average difference of almost 7- fold in terms of IgG producing hybridomas and almost 100-fold difference in the number of antigen-specific clones. Importantly, not all genes were affected equally and the in vitro data were generated using a cell line derived from a different mouse strain than used for the immunization studies. Perhaps a subset of genes induced by interferons plays an important role in B cell activation and development or the B cell response to IFN-α and IFN-β varies depending on the strain of mouse.
Selective ablation of the YxxM motif of IL-7R alpha suppresses lymphomagenesis but maintains lymphocyte development (38.5)
Authors: Osborne Lisa , Duthie Kia A , Gascoyne Randy , Abraham Ninan 
Published: January 2023

Abstract
Lymphocyte homeostasis is exquisitely sensitive to the cytokine interleukin (IL)-7. Loss of IL-7 signaling prevents lymphocyte development whereas excess IL-7 causes murine lymphoma and has been detected in several human lymphomas. We have previously shown that targeted disruption of the Y449xxM motif of the IL-7 receptor alpha (IL-7Rα) in a knock-in mouse model (IL-7Rα449F) has minor effects on lymphocyte production, but interferes with activation of survival effectors. We hypothesized that targeted signal ablation would selectively affect lymphocyte transformation. To address this, IL-7Rα449F mice were crossed with two lymphomagenesis models, transgenic (Tg) IL-7 and Eμ Myc mice. We found that loss of IL-7Rα Y449 signaling was sufficient to reverse the developmental aberrations induced by both the IL-7 and Eμ Myc transgenes, prevented Tg IL-7 mediated T and B lymphocyte transformation and significantly decreased development of Eμ Myc-induced B cell tumors. We show that the IL-7Rα449F mutation is essential for Tg IL-7 mediated up-regulation of pro-survival Bcl-2 family members, and for rapid cycling of bone marrow progenitor B cells induced by Eμ Myc. This study highlights the therapeutic potential of targeting the IL-7Rα Y449xxM motif or its downstream effectors in treatment of human lymphocyte malignancies.
Research supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and the Michael Smith Foundation for Health Research.
Insight into Mechanism of IL-2-Induced Toxicity Provides Rationale for Improved Treatment Strategy using IL-2/mAb Complexes (38.8)
Authors: Boyman Onur , Krieg Carsten , Létourneau Sven , Pantaleo Giuseppe 
Published: January 2023

Abstract
IL-2 immunotherapy is used against certain metastatic cancers and for patients infected with human immunodeficiency virus. However, administration of IL-2 can lead to serious side effects including pulmonary edema, the pathogenesis of which is ill-defined. Here, we provide data showing that IL-2 may bind directly to CD25 on lung endothelial cells and thus cause toxicity and pulmonary edema. Thus, lung endothelial cells express CD25 under steady-state conditions, and expression levels of CD25 on these cells increase in vivo upon injection of mice with IL-2. Activation of CD25+ lung endothelial cells and of IL-2 receptor-positive NK cells and T cells leads to pulmonary edema upon IL-2 treatment. Significantly, co-administration of anti-CD25 antibody along with IL-2 treatment is able to completely abrogate IL-2-induced pulmonary edema despite considerable proliferation of NK cells and T cells. Similarly, knocking out CD25 on non-immune cells or obscuring the CD25-binding epitope of IL-2 by the use of selective immune complexes of IL-2 plus anti-IL-2 antibody (IL-2/mAb) is able to prevent IL-2-induced pulmonary edema. Notably, IL-2-mediated toxic effects are also evident on a human lung cell line and can be abrogated using the anti-CD25 antibody daclizumab or IL-2/mAb complexes. Moreover, IL-2/mAb complexes are very efficient in generating anti-tumor responses in vivo against syngeneic local or metastatic tumor nodules. Thus, CD25+ endothelial cells play a crucial role in IL-2-mediated vascular leak syndrome and this can be circumvented by the use of IL-2/mAb complexes.
Inhibition of IFN-γ responses in human choriocarcinoma cells by PTPs (166.18)
Authors: Bushway Meghan , Weise Paige , Grace Daniel , Olsen Keith , Choi Jason , Murphy Shawn 
Published: January 2023

Abstract
Placental trophoblast cells (TBCs) form the fetal component of the placenta, and are the only blastocyst-derived cells in direct contact with maternal blood and thus immune system. Interferon-γ (IFN-γ) is a pro-inflammatory cytokine that is critical for the activation of both innate and adaptive immune responses, inhibition of cell proliferation, and induction of apoptosis. Interestingly, IFN-γ is present in the uterus during normal pregnancy and levels can be further enhanced upon intrauterine infection. Despite the presence of IFN-γ in the uterus, human TBCs do not express either MHC class Ia or class II antigens and are resistant to IFN-γ-mediated apoptosis. We previously demonstrated that TBCs are hypo-responsive to IFN-γ due to protein tyrosine phosphatase (PTP)-mediated inhibition of the JAK-STAT-1 pathway. These results suggest that inhibition of IFN-γ signaling in TBCs is due to differential regulation of PTP activity. In most cell types, PTPs are constitutively active and are transiently inactivated by reactive oxygen species that are generated in response to ligand binding. Our current studies suggest that SHP-2 and/or PTP-1B are responsible for inhibiting IFN-γ responses in human TBCs. Moreover, our data demonstrate that human TBC-derived choriocarcinoma cells produce H2O2 in response to IFN-γ. Furthermore, studies in which TBCs were exposed to exogenous H2O2 or antioxidants suggest that lack of H2O2 production is not the basis for differential PTP activity.
IL-17 and IL-22 induced inhibitor of nuclear factor κB kinase-α (IKKα) expression in HaCaT human keratinocyte cell line (166.19)
Authors: Lee Kyung Ho , Cho Kyung-Ah , Kim Jin-Young , Woo So-Youn 
Published: January 2023

Abstract
The pathogenesis of psoriasis may involve the IL-23 and Th17-mediated immune responses. Th17 cells secret IL-17 and IL-22 which mediates dermal inflammation and acanthosis. As IKKα has been previously identified as a primary regulator of keratinocyte differentiation and proliferation, we proposed that IL-17 and IL-22 might affect keratinocyte differentiation by changing the expression of IKKα. We employed HaCaT cells maintained culture medium at a low calcium concentration (0.06 mM) and induced differentiation by switching high concentration (2.8 mM) media with IL-17 or IL-22, then compared IKKα expression and the cell cycle. We employed reconstituted human epidermal skin (Neoderm) and mice ears for the in vivo studies. Elevated calcium concentration induced IKKα expression and terminal differentiation with cell cycle arrest in HaCaT cell cultures. Moreover, IL-17 and IL-22 treatment also induced IKKα in HaCaT cells and reconstituted human epidermis. IKKα induction was also noted following the injection of IL-17 and IL-22 into mice ears. Although the induction of IKKα was accompanied by keratinocyte differentiation, IL-17 and IL-22 did not affect calcium-mediated differentiation or the cell cycle. Rather, IL-17 and IL-22 appear to contribute to inflammation occurring via the induction of IKKα from keratinocytes or skin layers.
Generation of memory TCRγδ T cells following oral L. monocytogenes infection (166.4)
Authors: Sheridan Brian , Pham Quynh-Mai , Lefrançois Leo 
Published: January 2023

Abstract
Listeria monocytogenes (LM) has been used as a model organism for studying T cell responses. However, the vast majority of LM immunological studies utilize inoculation routes other than oral. The oral infection studies here utilize a recombinant LM that expresses an internalin A protein with high affinity for mouse E-cadherin thus mimicking the physiologic route of infection in humans. Our findings reveal a remarkable mucosal TCRγδ T cell response to oral LM infection, whose kinetics mimicked an adaptive T cell response. The responding TCRγδ subset was polyfunctional and was comprised of both IL-17 and IFNγ producers and notably, IL-17/IFNγ double producers. They appeared distinct from “innate” TCRγδ IL-17 producers which are present early after infection and in peripheral lymph nodes of naïve mice. Moreover, this phenotypically and functionally distinct subset of mucosal TCRγδ T cells were retained long-term and underwent a recall response upon oral challenge similar to that of a TCRαβ T cell recall response. However, memory TCRγδ T cells failed to expand following iv rechallenge, suggesting tissue-specific mechanisms regulate their ability to mount a secondary response. Very little is known regarding the anatomy of TCRγδ T cell responses and our results identify a bona-fide mucosal memory TCRγδ T cell population following oral LM infection. With this model we can address novel questions regarding the induction of specialized TCRγδ subsets and the development of memory.
Negative regulation of autoreactive B cell activation by integrin CD11b molecule (167.13)
Authors: Ding Chuanlin , Yan Jun 
Published: January 2023

Abstract
The immunological hallmark of systemic lupus erythematosus (SLE) is a loss of immune tolerance and B cell hyperactivity. Recent studies demonstrated an association between the variant of the integrin-α-M (ITGAM, also called CD11b) gene and SLE susceptibility. However, how CD11b regulates disease pathogenesis remains elusive. We found surprisingly that B cells from CD11b knock out (KO) mice exhibited hyperproliferative responsiveness to B cell receptor (BCR) cross-linking. CD11b KO autoreactive B cells had the decreased tyrosine phosphorylation including Lyn and PLCγ2 and increased p38 MAKP. Moreover, CD11b deficiency promoted B cell survival which was associated with increased BCL-xl expression. In vivo engagement of BCR by apoptotic cells resulted in significantly increased autoAb production in CD11b KO mice. Furthermore, we found that BCR cross-linking could induce CD11b activation and modulate CD11b-medited phagocytosis, suggesting ‘out-side-in’ activation of CD11b integrin by BCR crosslinking. Taken together, these results reveal the interaction between CD11b integrin and BCR signaling pathways and suggest the critical role for CD11b molecule in maintaining autoreactive B cell tolerance (This work was supported by the Alliance for Lupus Research).
Exosomes from mouse bone marrow-derived mesenchymal stem cells (mMSCs) mediate a potent immunosuppressive function (167.15)
Authors: Kim Sueon , Shin Jin-Young , Kim Yong-Hee , Kim Chung-Gyu 
Published: January 2023

Abstract
Mouse mesenchymal stem cells (mMSCs) have been reported to control the inflammation in the central nervous system (CNS) and alleviate the disease severity in the neurodegenerative disease models such as experimental autoimmune encephalitis (EAE). Although increasing evidences suggest that these cells can contribute to modulate immune responses, the underlying mechanisms are not fully understood. In this study, exosomes were purified from the culture supernatant of mMSCs using ultracentrifugation under sucrose cushion and tested for their immunosuppressive effects toward activated T cells. Exosomes exhibited potent suppressive effects on T cell proliferation through cell cycle arrest and apoptosis as revealed by thymidine incorporation and flow cytometric analyses. Importantly, exosome-depleted culture supernatant (EDCS) had no such effect. To prove exosome's effect in vivo, EAE was induced in four cohorts of mice and exosome, exosome-enriched, exosome-lowered by methyl-β-cyclodextrin (MβCD) culture supernatant or saline was treated to each group from disease initiation phase. Results showed that exosome and exosome-enriched culture supernatant, but not exosome-lowered culture supernatant can ameliorate autoimmune symptoms. In conclusion, our results suggest that exosomes secreted from mMSCs mediate immuno suppressive function.
MicroRNA-29 controls Th1 bias of CD4+ T cells in multiple sclerosis (167.5)
Authors: Smith Kristen , Guerau-de-Arellano Mireia , Williams Jessica , Cox Gina , Croce Carlo , Racke Michael , Lovett-Racke Amy , Whitacre Caroline 
Published: January 2023

Abstract
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system initiated by autoreactive CD4+ T cells of a T-helper (Th)1 and Th17 phenotype. Identifying novel factors that control Th differentiation will lead to a better understanding of MS pathogenesis and the development of new therapeutic strategies. MicroRNAs (miRs) are small non-coding RNAs that negatively regulate post-transcriptional gene expression. Dicer-deficient CD4+ T cells that lack miRs produce more of the Th1-associated cytokine IFN-γ; however, the specific miR(s) responsible for controlling Th1 programming have not been defined. Using in silico target prediction algorithms, we identified miR-29 as a factor that could potentially regulate multiple genes in the Th1 pathway. We confirmed that miR-29 directly targets T-bet and IFN-γ, and gain- and loss-of-function experiments demonstrated the ability of miR-29 to modulate Th1 polarization. Importantly, we found that naïve CD4+ T cells from MS patients express lower basal levels of miR-29 than controls. We further established an inverse relationship between basal expression of miR-29 and expression of T-bet/IFN-γ following activation of MS patient T cells. These results identify miR-29 as a novel regulator of Th1 differentiation and function, and implicate low miR-29 as an MS susceptibility factor. Restoring miR-29 may therefore be a powerful therapeutic modality in MS and other Th1-driven autoimmune diseases.