bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD103 promotes the proinflammatory response of gastric resident CD4+ T cell in Helicobacter pylori- positive gastritis
Authors: Wu Yongjian , Ming Siqi , Liang Siping , Wu Minhao , Chen Peiyu , Geng Lanlan , Gong Sitang 
Published: January 2023

Abstract
As an integrin found on T cell residence, CD103 is associated with the CD8+ T cell response in allogeneic transplant rejection, autoimmune diseases and cancer, but its role in infection and inflammation remains unclear. In this study, biopsy specimens of the gastric mucosa were obtained from patients with H. pylori-positive gastritis. We found that CD103 was highly expressed in CD4+T cells of the gastric mucosa from patients with H. pylori-positive gastritis. Mucosal resident CD103+CD4+T cells exhibited an increase in the CD45RO+CCR7− effector memory phenotype and high expression of the chemokines CXCR3 and CCR9 compared with those in CD103−CD4+ T cells. An In vitro coculture study demonstrated that H. pylori-specific antigen CagA/ VacA-primed dendritic cells (DCs) induced proliferation as well as IFN-γ, TNF and IL-17 production by CD103+CD4+ T cells from patients with H. pylori-positive gastritis. Furthermore, blocking CD103 with a neutralizing antibody reduced proliferation and IFN-g, TNF and IL-17 production by CD103+CD4+ T cells cocultured with DCs. Moreover, immunoprecipitation revealed that CD103 interacted with TCR α/β and CD3ζ, and activating CD103 enhanced the phosphorylation of ZAP70 induced by the TCR signal. Finally, increased T-bet and Blimp1 levels were also observed in CD103+CD4+ T cells, while activating CD103 increased T-bet and Blimp1 expression in CD4+ T cells. Our results explored the function of CD103 in gastric T cells from patients with H. pylori-positive gastritis, which may provide a therapeutic target for the treatment of gastritis
Mechanism of Microvascular Endothelial Cells Protected by Pulsatillae Decoction Activated Neutrophils to Kill Bacteria
Authors: He shangwen , Liu Xiaoye , Li Qiuyue , Zhang Hui , Hou Silu , Xu Yuanyuan , Dong Hong 
Published: January 2023

Abstract
Neutrophils play critical a role in bacterial infection and tumor immunity. The migration of neutrophils across microvascular endothelial cells has been a focus of increased interest within the past decade. A traditional Chinese herbal formula, Pulsatillae Decoction (PD), has the effects of improving the permeability of MVECs, inhibiting apoptosis and enhancing cell activity. But there are very few studies linking the three, and the effect of PD on the bactericidal function of PMNs transendothelial migration is unclear. To investigate the protective effect of PD on the damage of Rat microvascular endothelial cells (RIMVECs) induced by LPS and it’s mechanism of activating neutrophils (PMNs) to kill bacteria by protecting RIMVECs, we established a model of LPS-induced RIMVECs injury and to evaluate the protection of PD against LPS-induced RIMVECs injury. We observed that LPS-injured RIMVECs inhibited the extracellular and intracellular bactericidal activity of transendothelial neutrophils, PD-protected RIMVECs promoted the extracellular and intracellular killing activity of transendothelial neutrophils and significantly increased NE and CG concentration in transendothelial neutrophils. In addition, SWATH/DIA proteome results showed that 11 consensus proteins were down-regulated in the model group and up-regulated in the treatment group, 23 consensus proteins were up-regulated in the model group and down-regulated in the treatment group. PD was likely to protect RIMVECs and activate the sterilization of PMNs by regulating these differential proteins.
CXCL10+ perivascular clusters nucleate Th1 cell tissue entry and activation in the inflamed skin
Authors: Prizant Hen , Patil Nilesh , Negatu Seble , Livingston Alexandra , Leddon Scott , Luster Andrew D , Fowell Deborah J 
Published: January 2023

Abstract
Efficient recruitment and correct positioning of T cells within infected peripheral tissues are crucial for pathogen clearance. Using a dual-chemokine reporter (Groom et Al. Immunity, 2012) mouse and intra-vital imaging, we identified a preferred tissue entry and accumulation site for effector Th1 cells, defined by clusters of CXCL9 and CXCL10 expressing hematopoietic cells, enriched with MHC-class-II+ cells, in restricted perivascular spaces within the inflamed dermis. Unbiased computational analysis of motility dynamics of antigen-specific Th1 cells within these clusters, revealed cell confinement characteristics. CXCR3 on Th1 cells and presence of cognate antigen were critical for persistence within clusters and T cell activation. Newly recruited Th1 cells strongly amplified CXCL9 and CXCL10 expression, mainly within skin monocyte-derived dendritic cells, in an antigen- and interferon-gamma-dependent manner, resulting in augmented chemokine clusters. Our data suggest a CXCR3-mediated mechanism of intrinsic amplification loop for optimal Th1 cell recruitment, positioning and activation in restricted antigen presentation sites within the inflamed skin.
Chemical modification strategies for photo-induced control of immune cell signaling
Authors: Perdue Lacey A , Do Priscilla , Chyong Andrew , Costanza Emma , Kim Hye Ryong , David Camille , Kellner Anna , Salaita Khalid , Lesinski Gregory , Porter Christopher C. , Dreaden Erik C. 
Published: January 2023

Abstract
Cytokine therapies show great potential to induce cancer immune elimination and have demonstrated therapeutic benefit in a subset of patients. However, controlling the pleotropic effects of these immune signal effectors is a challenge. Here, we present an approach to enable optical control of cytokine activity by caging the activity of these proteins via labeling with wavelength-specific, photo-labile polymers (i.e. photo-caging). We create a system to measure light-induced polymer cleavage (uncaging) through fluorescence dequenching and establish: high wavelength-selectivity, protein activation through tissue mimics, and micrometer-scale uncaging resolution (via photopatterning). We focus on cytokines IL-2, IL-12 and IL-15 and demonstrate ability to reversibly modulate cytokine size and activity. We show photo-caging increases cytokine size by up to 20 fold, resulting in increased serum half-life. Additionally, cytokine activity (via T-cell proliferation) is blunted by 1,000 fold and near fully recovered through light-induced uncaging. Affinity measurements demonstrate photo-caging disrupts the bias of IL-2 towards IL-2Rα expressed on immunosuppressive T-regulatory cells. Further, photo-caging negates the ability of IL-2 to increase antigen specific (OT-1) cell activation, but is restored upon uncaging. In summary, we present the synthesis and therapeutic potential of these optically activated cytokines. In future studies we aim to use cytokine photo-caging as a means to provide new insights into the mechanics of cancer immune elimination and achieve tissue exclusive activation by exploiting spatially and temporally constraining cytokine activation in chip-based organoids and in vivo cancer models.
Inflammation impairs IL-2R signaling in regulatory T cells
Authors: Hsiung Sunnie , Malek Thomas R 
Published: January 2023

Abstract
Low-dose IL-2 is a promising therapy to boost Tregs in autoimmune diseases. Inflammation accompanying autoimmunity destabilizes Tregs to diminish their function. Here we explored how the extent of acute inflammation induced by LPS and poly(I:C) and of chronic inflammation induced by immunization with MOG and pertussis toxin (MOG/PT) affects IL-2R signaling in Tregs. IL-2-dependent pSTAT5 was significantly, but transiently, reduced in Tregs ex vivo from C57BL/6 mice exposed to LPS and MOG/PT, but not poly(I:C). LPS and PT, but not poly(I:C), induced inflammation through TLR4. IL-2-dependent pSTAT5 was also decreased in WT mice treated with only PT or in TLR4 Treg-conditional knockout mice treated with LPS. Thus, impaired IL-2R signaling is likely dependent on monocyte-derived inflammatory mediators through TLR4 signaling. LPS also decreased Treg proliferation as measured by Ki67 and increased CD69 expression. In contrast, these changes were not seen after treatment with poly(I:C) and MOG/PT, consistent with inflammation affecting Tregs independent of lower IL-2R signaling. When Tregs from LPS-treated mice were stimulated with IL-2 in vitro, pSTAT5 was induced, indicating that Tregs are not intrinsically unable to respond to IL-2. RNAseq of Tregs from LPS-treated mice revealed substantial changes in their transcriptome, suggesting a potential complex mechanism that impairs IL-2R signaling and other activities in Tregs in vivo. Our data support a model where inflammation lowers IL-2R signaling in Tregs by decreased IL-2 in the Treg microenvironment and causes other induced changes in Tregs to lower their function. Thus, a beneficial feature of low-dose IL-2 therapy may be to counteract negative effects of inflammation on Tregs.
IL-9 Represses Intestinal Granzyme A Positive CD4 T Cells in Mice with Allergic Airway Inflammation
Authors: Hayes Tristan A , Ulrich Benjamin J , Fu Yongyao , Pajulas Abigail , Kaplan Mark H 
Published: January 2023

Abstract
Mediated by immune responses in the airways, symptoms of allergic airway diseases include shortness of breath, difficulty breathing, and wheezing. Responses in distant tissues, such as increased lymphocyte proliferation and cytokine secretion, are also exhibited. How airway sensitization mediates these distant effects is unclear. We recently described the development and function of granzyme A-expressing T cells that control intestinal inflammation. Using models of chronic and memory allergic airway inflammation, we now show that a granzyme A expressing CD4 T cell population in the intestine increases during these diseases. This response is amplified in mice that lack IL-9 signaling through a deficiency in IL-9 receptor levels (IL9RKO) or receive an IL-9 antibody blockade. In a chronic intranasal allergen challenge model, we saw elevated levels of granzyme A expressing CD4 T cells in IL9RKO mice when compared to wild-type controls. In a memory internasal allergen model using wild-type mice (chronic allergen exposure, followed by an allergen-free rest period, and an allergen re-exposure), granzyme A expressing cells in the intestine were increased upon IL-9 antibody blockade. Blocking IL-9 or administering IL-9 to naïve mice or cell cultures that generate granzyme A expressing T cells did not affect cell prevalence. Therefore, concurrent allergic airway inflammation seems to be required for the proliferation of these granzyme A expressing T cells. Together, these studies suggest that allergic airway inflammation increases granzyme A expressing CD4 T cells in the intestine and that IL-9 attenuates this effect. Moreover, these results show that allergic airway inflammation impacts immunity at a distant mucosal site.
Autocrine and paracrine IL-2 signals collaborate to regulate distinct phases of CD8 T cell memory
Authors: Kalia Vandana , Yuzefpolskiy Yevgeniy , Vegaraju Adithya , Smith Kendall A , Sarkar Surojit 
Published: January 2023

Abstract
Differential IL-2 signaling is implicated in memory CD8 T cell fates. Autocrine IL-2 production is a hallmark of polyfunctional, long-lived lymphoid memory cells. Whether the IL-2 signals perceived by CD8 T cells come from autocrine or paracrine sources, the timing of these signals, and their differential impact on the qualitative outcomes of CD8 T cell responses are not clearly understood. We used two distinct models of germline and conditional autocrine IL-2 ablation in post-thymic CD8 T cells to specifically dissect the requirement and timing of autocrine IL-2. Our studies show that autocrine IL-2 is uniquely required during primary CTL responses to program the key memory property of robust recall responses. Ablation of autocrine IL-2 in fully differentiated wild type memory cells immediately prior to rechallenge did not impact their recall expansion potential. Furthermore, we found that paracrine IL-2 could effectively supplant autocrine IL-2 for primary expansion, effector differentiation and memory maintenance, but not recall expansion. Likewise, our data highlight the redundancy of autocrine and paracrine IL-2 in optimally driving equivalent metabolic programs associated with effector and memory states. While CD4 licensing of DCs is needed for optimal programming of autocrine IL-2 in CD8 T cells, we found that the requirement for CD4 help is less critical for autocrine IL-2 production in the context of inflammatory infections. These findings have implications in adoptive T cell immunotherapies where expansion of engineered cells is largely driven by paracrine IL-2, which can potentially impact their long-term sentinel function.
Interleukin 2 enhances and sustains IFNy induced STAT1 activation in subpopulations of CD4+ and CD8+ T lymphocytes in untreated relapsing remitting multiple sclerosis (RRMS) patients
Authors: Pope Brandon J , Sharma Vishal , Meador William , Reynolds Richard , Bridges S. Louis , Raman Chander 
Published: January 2023

Abstract
Multiple sclerosis (MS) is the most common demyelinating disorder in adults, where 85 percent of patients exhibit relapses, followed by remission (RRMS). IFNy administered to RRMS patients increases relapse rate. IFNy producing myelin specific T lymphocytes correlate with functional impairment in MS. RRMS derived neuronal lesions show increased expression of IFNy induced genes on microarray analysis, compared to controls. At time of diagnosis, we observed comparable levels of IL2 and IFNy in the plasma of RRMS patients. Since IL2 constrains differentiation of specific CD4+ effector lineages (i.e. Th17, Tfh) in the context of autoimmunity, we predicted that its expression was an effort to counteract IFNy signals. To test for this possibility, we interrogated the effect of IL2 on IFNy induced activation of STAT1 in subpopulations of CD4+ and CD8+ T cells (effector, memory, and regulatory) from newly diagnosed RRMS patients. In all CD4+ and CD8+ T cell populations from RRMS, IFNy induced activation of STAT1 that peaked at 1h followed by decay at subsequent timepoints. In a subset of RRMS patients, costimulation with IFNy and IL2 resulted in enhanced and sustained activation of STAT1 in CD4+ and CD8+ naïve and effector T cells, CD4+ memory T cells, and Treg cells. IFNy had no effect on IL2 induced STAT5 activation. From these results, we infer that in some MS patients IL2 will collaborate with IFNy to enhance effector T cell activation to promote autoimmune neuroinflammation. These results suggest that low dose IL2 therapy could exacerbate RRMS disease severity in such patients.
Active learning about the dynamic and complex nature of CD4+ T cell differentiation with computer network modeling and simulations
Authors: Helikar Tomas , Helikar Resa M , Brown Deborah M 
Published: January 2023

Abstract
CD4+ T cells provide cell-mediated immunity in response to various antigens. During an immune response, naïve CD4+ T cells differentiate into specialized effector T helper cells (e.g., Th-1,-2,-17, etc.), and induced regulatory (iTreg) T cells. Their proper response to pathogens is governed by complex, non-linear dynamic networks consisting of various types of cells and their associated communication mediators (cytokines). The regulation of CD4+ T cell differentiation is a major topic of many post-secondary immunology-related courses.
However, the traditional lecture and textbook-based learning format in these (and other life sciences) courses makes it challenging for students to fully conceptualize and appreciate the complex and dynamic nature of such processes. We have developed a new learning approach that enables students to build, simulate, and investigate computational models of processes embedded in biological systems. This method is facilitated through an easy-to-use software, Cell Collective (https://cellcollective.org), that makes computational modeling accessible to any student and instructor (i.e., no prior computational modeling experience is necessary). The simulation lessons have been designed to be turn-key, self-contained, and adoptable by any instructor without the need to modify their syllabus, and with a minimal learning curve. They can be used in-class, assigned as homework, as well as deployed as extensive lab investigations. Here, we will present a new modeling and simulation lesson that enables students to learn about the dynamic complexities of CD4+ T cell differentiation, such as the effects of different cytokines and their dosage on the differentiation outcome, feedback loops, etc.
Development of Curriculum Guidelines for Undergraduate Immunology Education –a Report by a Task Force on Undergraduate Immunology Curriculum Guidelines
Authors: Justement Louis B , Bruns Heather A. , Elliott Samantha , Sletten Sarah , Sparks-Thissen Rebecca , Condry Danielle , Wisenden Brian , Lal Archana , Paustian Timothy , Mixter Philip F , Taylor Rebekah , Pritchard Rachel , Vanniasinkam Thiru , Dorsam Glenn , Freier David , Pandey Sumali 
Published: January 2023

Abstract
Until recently, immunology education was primarily introduced at the graduate level. However, in the age of modern medicine, a fundamental understanding of the immune system is becoming increasingly critical. The immune system affects every organ system in the body, and entails many concepts that are critical for training students who wish to pursue health professions or research-intensive careers. In addition to medicine, ecologists and computer scientists have lately been attracted to the field to investigate problems related to ecoimmunology or for development of machine learning tools for disease modeling. The need to focus on undergraduate immunology education has been strongly recognized and advocated for in several recent publications. In response to this need, we, a newly formed task force of undergraduate immunology educators, have identified fundamental concepts that are critical to the understanding of immunology for undergraduate students. We have aligned these fundamental statements with the overarching concepts described in the AAAS report “Vision and Change in Undergraduate Biology Education: A Call to Action”, and are now gathering feedback on these guidelines from undergraduate educators at large. Establishment of these guidelines is consistent with new pedagogical practices that emphasize conceptual understanding of the subject over rote memorization and provides a framework needed to introduce students to immunology. The goal of this project is to solicit feedback from the immunology community in an effort to achieve consensus regarding the fundamental concepts in immunology that are critical for STEM-focused students to comprehend.
Improving the computational reproducibility of immunological research
Authors: Anderson Brooke , Lyons Michael , Henao-Tamayo Marcela I , Juarrero Mercedes Gonzalez , Robertson Gregory 
Published: January 2023

Abstract
Many excellent and free training resources exist to improve the computational reproducibility of biomedical research. However, most of these materials target researchers at the stage of data analysis, and they typically provide much less guidance on principles and techniques to improve the reproducibility of the earlier steps of experimental data recording and experimental data pre-processing that are critical for ensuring the reproducibility of immunological research. Many common existing practices---including the use of spreadsheets with embedded formulas that concurrently record and analyze experimental data, problematic management of project files, and reliance on proprietary, vendor-supplied point-and-click software for data pre-processing---interfere with the transparency, reproducibility, and efficiency of laboratory-based immunological research projects. Under an NIH grant, we are creating new training modules as a resource for laboratory-based biomedical researchers to learn how simple computational principles can improve reproducibility at the stages of data recording and pre-processing in immunological research. In this poster, we will highlight several simple approaches that we have identified through this project to improve the reproducibility of immunological research, including strategies for re-designing data collection spreadsheet templates to more easily integrate into a reproducible data analysis workflow and the use of reproducible reporting tools within a laboratory setting.
Use of crossword puzzles: Filling the rows and columns to promote student engagement in an Immunology class
Authors: Kucknoor Ashwini S 
Published: January 2023

Abstract
Although crossword puzzles have been around for decades, researchers still study their use in the classroom. Previously, educational crossword puzzles only came in mass-produced student workbooks, which meant educators were unable to adapt them for the needs of their classroom. Although the research for teaching with educational crossword puzzles covers all sorts of subjects from ESL to Chemistry and widely used in grade schools mainly as a tool to learn vocabulary, studies find that crossword puzzles can help introduce and reinforce concepts for any subject. The bulk of undergraduate teaching is usually done through traditional PowerPoint lecture presentations in majority of the universities, which fails to encourage knowledge retention and learning. In contrast, recent studies have shown that the implementation of active- and collaborative learning, using games, music and puzzles promote stimulating environment to enhance student engagement and active participation of students during lecture. Active learning exercises provide major benefits such as the development of critical thinking, communication skills, and increasing motivation to learn. To this end, I have incorporated the use of crossword puzzles in my Microbiology and Immunology courses recently. I have developed questions covering new vocabulary or technical terminology, ability to distinguish between similar terms, evaluating options, and developing logical thinking for both Immunology and Microbiology concepts. I have mainly used the crossword puzzles to quickly summarize and emphasize the important facts and concepts delivered during regular lectures. The details of how this was used, and more ways by which this can be adopted in a course will be discussed.
METABOLIC INSULTS ELICIT EPITOPE-DEPENDENT IMMUNE AUTOREACTIVITY AGGRAVATING HEPATIC DAMAGE IN TYPE 2 DIABETES
Authors: Santambrogio Laura , Clement Cristina C , Nanaware Padma , Stern Lawrence 
Published: January 2023

Abstract
A diet rich in saturated fat and carbohydrates causes low-grade chronic inflammation in several organs including the liver, ultimately driving non-alcoholic steatohepatitis. The environment-driven lipotoxicity and glucotoxicity induces liver damage, which promotes dendritic cell adjuvanticity and generates an MHC-II immunopeptidome enriched of peptides derived from proteins involved in cellular metabolism, oxidative phosphorylation, and stress responses. Here, we demonstrate that metabolic insults promote the presentation of nested T and B cell epitopes from protein disulfide isomerase family A member 3 (PDIA3, which is involved in immunogenic cell death) on MHC Class II, ultimately supporting pathogenic autoreactivity. Additionally, PDIA3-driven T cell responses infiltrating the hepatic parenchyma, favored the release of TH1 and TH17 pro-inflammatory cytokines and, PDIA3-driven B cell responses were associated with antibodies that aggravated hepatic toxicity in mice subjected to high-fat and high-sucrose diet. Increased humoral responses to PDIA3 were also observed in patients with chronic inflammatory liver conditions including autoimmune hepatitis, primary biliary cholangitis and type 2 diabetes. Altogether our data indicate that metabolic insult caused by high-sucrose diet, cause tissue damage, which, by supplying PDIA3 T cell and B cell epitopes further contributes to epitope-dependent pathogenic immune autoreactivity
Supported by NIHAI146180 and NIH AI137198