bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune signatures of Alzheimer’s disease: profiles of neutrophils. (HUM1P.301)
Authors: LE PAGE Aurélie , Lamoureux Julie , Bourgade Karine , Frost Eric , Dupuis Gilles , Fulop Tamas 
Published: January 2023

Abstract
Alzheimer's disease (AD) is the most common form of dementia. Amyloïd plaques accumulation and microbial infections have been proposed as an important components of AD aetiology. Defects in amyloïd-β clearance by monocyte/macrophage/microglia, imply that the immune system may participate in development and progression of AD. Phenotype and functional analysis of polymorphonuclear neutrophils (PMN) in peripheral blood were performed by flow cytometry. Our cohort of patients comprised amnestic Mild Cognitive Impairment (aMCI) (n = 10), mild stage AD (mAD) (n = 10) and healthy elderly controls (n = 10). aMCI patients had memory impairment but no functional disorders. However, these patients have a 50% chance of developing AD within 3 years following the diagnostic. PMN number was unchanged between the three groups. In contrast, the CD177+ population was significantly increased in mAD patients (p &lt; 0.05). Phagocytosis of opsonized bacteria was less in aMCI and AD patients than controls. This observation was associated in aMCI with a decrease in CD33 (siglec 3) and complement receptor for C5A expression. Decreased expression of CD14 (a pattern recognition receptor), CD15 (carbohydrate adhesion molecule) and CD16 (FcγRIII) expression was found in mAD patients. Our results describe for the first time alterations of neutrophils in aMCI patients. PMN analysis may provide a useful tool in early identification of AD patients.
Peripheral inflammation reflects cortical Aβ load in patients with amnestic mild cognitive impairment (HUM1P.302)
Authors: Stowe Ann , Ireland Sara , Ortega Sterling , Chen Ding , Huebringer Ryan , Cullum C , Greenberg Benjamin , Monson Nancy , Zhang Rong 
Published: January 2023

Abstract
The National Plan to address Alzheimer’s disease (AD) underscores the urgent need for the prevention and treatment of AD, especially with a new patient diagnosed in the U.S. every 67 seconds. We recently published data showing increased levels of central nervous system inflammation in patients with amnestic mild cognitive impairment (aMCI), a precursor disease to Alzheimer’s disease (AD). We found that lymphocytes and pro-inflammatory cytokines in the cerebrospinal fluid (CSF) of aMCI patients were elevated similar to or exceeding those found in patients with multiple sclerosis. To determine any potential contribution of central and peripheral inflammation to AD pathology, we analyzed within-patient leukocyte populations and correlated these measures with brain amyloid (Aβ) burden, quantified by PET imaging at time of CSF and blood collection. Fifteen patients (55-76 yr old) and/or their study partners signed written informed consent. Age significantly increased plasmablast representation and decreased NK T cell populations in the CSF, but this did not reflect brain Aβ levels. Independent of patient age, higher cortical Aβ levels were significantly correlated to increased CD8 T cell and decreased CD4 T cell populations in the peripheral blood. Additionally, peripheral memory B cells increased with Aβ burden but not with age. These data suggest a potential role of the adaptive immune system in the development of cortical Aβ burden at a preclincial stage of AD.
Low ambient oxygen prevents atherosclerosis (HUM1P.254)
Authors: Kang Ju-Gyeong , Sung Ho Joong , Amar Marcelo , Remaley Alan , Springer Danielle , Kwon Jaeyul , Chen Jichun , Wang Pingyuan , Hwang Paul 
Published: January 2023

Abstract
Large epidemiolgic studies show that living at high altitude, which decreases oxygen exposure, is associated with reduced cardiovascular and cancer mortality. However, some experimental data show that acute hypoxia exposure can increase atherosclerosis by worsening inflammation and blood lipid profiles. We sought to address these disparate observations by chronically controlling the oxygen exposure of ApoE-/- mice and examining its effect on atherosclerosis. Herein, we report that reducing oxygen exposure by 50% caused a marked decrease in aortic atherosclerosis, associated with the inhibition of pro-inflammatory cytokines in circulation and increased anti-inflammatory IL10 levels in aortic tissue. We further show that the expression of IL10, well established to prevent atherosclerosis, was induced by low oxygen in a hypoxia inducible factor-1α (HIF1 α) dependent manner. We propose that this anti-inflammatory mechanism may contribute to the lower incidence of ischemic heart disease in populations living at high altitudes and suggest a potential therapeutic pathway for disease prevention.
Increased sensitivity of peripheral CD27+ memory B cells to Fas-induced apoptosis contributes to their disappearance in cirrhosis (HUM1P.309)
Authors: Kaplan David , Chang Li-Yuan , Tanoue Shiroh , Li Yonghai 
Published: January 2023

Abstract
Liver cirrhosis is associated with a 70% decrease of peripheral CD27+ memory B cells. The mechanism for CD27+ B-cell loss in cirrhosis remains unknown. We hypothesize that increased sensitivity to fas-mediated apoptosis leads to reduced peripheral CD27+ B-cells survival. Methods: Ex vivo B-cell fas-receptor (CD95) expression and in vitro measurement of spontaneous and fas-induced apoptosis (annexin V/PI) in 11 cirrhotic (CIR) and 11 healthy donors (HD). We found that expression of CD95 was significantly higher in CD27+ B cells than in CD27- B-cells in both CIR and HD (CIR, 50.2% versus 3.8%, p&lt; 0.0001). The ex vivo percentage and gMFI of CD95 on CD27+ B-cells was significantly higher in CIR than HD (CIR 50.2% versus HD 34.6%; CIR 624 versus HD 337, p&lt;0.02). Surprisingly, ex vivo CD27+ B cells were resistant to fas-mediated apoptosis in both CIR and HD. Anti-CD40 activation of sort-purified CD27+ and CD27- B cells resulted in upregulation of CD95 (1.05-1.17-log-fold) to similar degrees in CIR and HD. Addition of agonist anti-fas resulted in significantly greater apoptosis in cirrhotic CD27+ B cells relative to HD (CIR 33.3% versus HD 18.5%, p=0.05). Conclusion: These data suggest that peripheral CD27+ memory B-cell in cirrhosis exhibit increased sensitivity to fas-induced apoptosis in an activation-dependent manner. This sensitivity may be associated with their reduced frequency in cirrhosis and possibly with resultant derangements of humoral immunity seen in cirrhosis.
Endoscopy and FACS analysis in classic and humanized murine models of GVHD (HUM1P.316)
Authors: Beal Dominic , Graham Sean , Van Dam Brett , Lyng Gregory , Sonis Stephen 
Published: January 2023

Abstract
It is perplexing that standard murine GVHD model endpoints of weight loss (WL) and composite clinical changes (CCC) often fail to respond to standard forms of therapy (tacrolimus and anti-p40 monoclonal antibody). To improve on the translatability of GVHD models we evaluated serial endoscopy as a means to directly assess injury and serial blood counts to predict onset of severe disease. Two models were used. CD3+ cells were magnetically depleted from bone marrow harvested from male Balb/c mice. Varying numbers of (depleted) bone marrow and splenocytes were then injected IV into lethally irradiated (8Gy) C57Bl/6 hosts. Serial endoscopy performed after GVHD onset (~2 weeks post transfer) demonstrated changes which strongly correlated with WL and CCC (R2=-0.84 and 0.79). Next we induced GVHD in a humanized model by the adoptive transfer of human PBMCs into severely immunocompromised mice (NSG). Serial blood draws demonstrated a strong correlation between peripheral blood human T cell (PBTC) numbers and WL and CCC (R2=-0.85 and 0.67 on day 42) suggesting that assessment of PBTC numbers may be applicable to the evaluation of therapies directly targeting these cell types. Day 7 human PBTC counts predicted final WL and CCC scores with high correlation (R2=-0.86 and 0.90) indicating that this metric can be used to stratify animals into groups prior to the onset of observable disease and treatment.
A transgenic mouse model correlates anomalous immune dynamics in human sickle cell disease (HUM1P.256)
Authors: Pryor Julianna , Collins Brittany , Joshi Sunil 
Published: January 2023

Abstract
Sickle cell disease, SCD, is an inherited blood disorder characterized by hardened, sticky C-shaped RBCs is a major cause of morbidity and mortality. It is the most prevalent genetic disease affecting 1/500 African Americans and 1/36000 Hispanics Americans, most residing in southeastern Virginia. Severe, frequent infections occur as a result of immune dysregulation associated with disease progression, impairing both innate and adaptive immunity. APCs such as DCs, B cells and macrophages express MHC II bind antigen that is recognized by TCR expressed on CD4+ Th cells. Thus, the interaction between receptor-ligand clusters on Th and APCs led to the activation of naïve CD4+ Th cells, stimulating the release of cytokines that influenced the activity of many cell types, including the NKT, CD8+ CTLs and the APCs that activated them. A “humanized” sickle mouse model of SCD was created by generating bone marrow chimeras using sickling mice donors and Pepboy recipients. We recently found that the transition from SPF to ‘dirty’, conventional, housing significantly dysregulated the immune system. These changes were characterized by a hyper-inflammatory state with the activation of innate-immune response, upregulation of TLR4, and loss of antigen-presentation machinery, loss of MHC II expression, with disease progression. Results indicate the loss of MHC II expression on APCs from various tissue of sickle mouse with the disease progression.
The ETS family transcription factors ETV5 and PU.1 co-regulate Th9 cell differentiation (HYP2P.334)
Authors: Hufford Matthew , Koh Byunghee , Pham Duy , Kaplan Mark 
Published: January 2023

Abstract
T helper 9 (Th9) cells, a CD4+ T cell subset characterized by their robust production of interleukin (IL)-9, can promote allergic inflammation in mice and are associated with atopic disease in humans. We have previously demonstrated that the E26 transformation-specific (ETS)-family transcription factor PU.1 is integral in Th9 mediated IL-9 production and is the only transcription factor, to date, that induces IL-9 production in another Th subset. Because conditional PU.1 deletion in T cells does not completely eliminate Th9 mediated IL-9 production, we investigated whether other ETS proteins were important transcription factors in Th9 cell development. Herein, we demonstrate that ectopic expression of ETS Variant 5 (ETV5) can also enhance Th9 cell differentiation and promote IL-9 production in Th2 differentiated cells. Conversely, conditional deletion of ETV5 impaired IL-9 production in Th9 cultures while promoting Th2 cytokine production. Unlike PU.1 that binds the Il9 promoter, ETV5 preferentially binds potential enhancer regions of Il9, and recruits distinct histone acetyltransferases from those recruited by PU.1. Finally, conditional deficiencies of both ETV5 and PU.1 in T cells effectively eliminated IL-9 production in Th9 cultured cells. The effects of deficiency in both factors are being tested in a model of allergic pulmonary inflammation. Collectively, these data indicate ETV5 and PU.1 co-regulate Th9 cell differentiation in partially non-redundant mechanisms.
miR-23~27~24 clusters restrict Th2 immunity and associated immunopathology during airway allergic reaction (HYP2P.335)
Authors: Wu Cheng-Jang , Cho Sunglim , Yasuda Tomoharu , Cruz Leilani , Lin Ling-Li , Miller Marina , Lee Hyang-Mi , Broide David , Rajewsky Klaus , Lu Li-Fan 
Published: January 2023

Abstract
MiRNAs (miRNAs) are important regulators in T cell differentiation and function. Here we show miR-23~27~24 clusters play a pivotal role in controlling type II immunity. Specifically, under Th2 polarizing condition, T cells with overexpression of miR-23~27~24 clusters exhibited reduced IL-4 secretion whereas T cells devoid of miR-23~27~24 clusters produced elevated amounts of IL-4. Further mechanistic studies revealed miR-24 and miR-27 could repress Gata3, a key regulator of Th2 cell differentiation through an indirect and a direct manner, respectively. Finally, by using an OVA-induced asthma model, we have shown that mice with T cell-specific ablation of miR-23~27~24 clusters developed a more severe airway inflammation characterized by increased IL-4 secretion, lung eosinophil infiltration, mucin production and serum IgE levels. Taken together, our studies identify a miRNA family with important biological function particularly in controlling Th2 immunity and suggest that a tight regulation of this miRNA family is required to maintain optimal effector T cell function and to prevent aberrant immune responses.
Deciphering ther ole of CD8+ T cells in allergic inflammation (HYP2P.339)
Authors: Anderson Erik , Kobayashi Takao , Iijima Koji , Kephart Gail , Chen Chien-Chang , Kita Hirohito 
Published: January 2023

Abstract
CD8+ T cells represent a relatively under studied cell type in allergic lung inflammation, despite their presence in the mucosal tissues. This is because CD8+ T cells are normally associated with a Th1 response as opposed to Th2 or Th17 responses, as are the most cases with allergic inflammation. However, recent papers have shown the production of Th2 and Th17 cytokines in these cells, yet knowledge of their physiological role in allergic inflammation is incomplete. The presence of IL-17 in asthma patients contributes to a severe, steroid resistant phenotype. Therefore, determining contributors of IL-17 and their physiological role is paramount to understanding the disease. Our preliminary data which suggests memory Tc17 cells are generated in CD4-/- mice when sensitized intranasally to ovalbumin with IL-33. We believe Tc17 cells are responsible for the inflammation because the inflamed lung tissue contained elevated IL-17, and stimulated T cells from inflamed tissue produced elevated levels of IL-17 as well. Additionally, we were unable to induce inflammation in Rag-/- mice or TCRβ-/- mice, which pinpoints the cell responsible to CD8+ T cells in CD4-/- mice. Using these mice to study an exaggerated phenotype will allow us to more easily detect the contributions that happen to a lesser degree in wild type animals. This work create a more complete picture of the disease environment and lead to therapies which can account for the contribution of this cell type.
The role of Notch signaling in T follicular helper cells during allergic immunity (HYP2P.326)
Authors: Dell Aringa Mark , Reinhardt Richard 
Published: January 2023

Abstract
The generation of Immunglobulin (Ig) E and high-affinity IgG1 by B cells is a hallmark of allergic inflammation. These hallmarks are heavily reliant on interactions with T follicular helper (Tfh) cells. A critical cytokine provided by Tfh cells to the germinal center B cells is Interleukin-4 (IL-4). The mechanisms controlling IL-4 production by Tfh cells remain unknown. Given that Notch signaling is required for the differentiation of Tfh cells and it is known to influence cytokine production in T cells, we hypothesized that Notch also plays an important role in regulating the function of Tfh cells. Here, we use intestinal helminth infection to characterize whether persistent Notch signaling is required to maintain Tfh cell fate and function during allergic immunity. Genetic deletion of Notch receptors in infected mice results in reduced IL-4 production by Tfh and Th2 cells. Conversely, over-expression of Notch signaling leads to increased IL-4 production by Tfh cells. However, increased Notch signaling also appears to alter Tfh cell fate and phenotype. In support, chemical inhibition of Notch signaling after Tfh differentiation results in decreased expression of the Tfh chemokine receptor, CXCR5 among IL-4 producing T cells in the lymph node. These findings suggest that Notch signaling is not only important for Tfh differentiation, but that strength of Notch signaling is important for regulating Tfh cell fate, function, and maintenance.
The effects of thermal Injury and sepsis on the production of leukocyte microvesicles (INC1P.360)
Authors: Babcock George , Domenico Karen , Robinson Chad 
Published: January 2023

Abstract
Microvesicles (MV) are membranous extra cellular vesicles derived from various cells following cell activation or apoptosis. MVs are typically defined as being from 0.1 to 1 µ in size. There have been several reports of biologically active MVs in the blood in certain clinical conditions. The goal of this study was to examine the effects of thermal injury plus sepsis on the number and type of MVs released from leukocytes. C57BL/J mice received 15% total body surface area burn followed by infection with Pseudomonas aeruginosa. At times post injury the blood and bone marrow were examined for MV expressing CD11b, CD19, CD34, CD41, and CD117 using flow cytometry. Generally,the absolute number of MV in the blood dropped following, however, the percentage of the various cell types changed. The percentage of CD11b, 34, and 42 increase slightly following burns but significantly following burn/infection.The absolute numbers of all MV dropped with the exception of CD 19 which increased both in percentage and absolute number in the burn group but not the burned/infected group. The absolute number of CD117+ MV increased significantly in the burn/infected group.The bone marrow remained relative stable with a slight increase in CD117+ MV. These data indicate that the pattern of MVs production changes following burn injury and burn infection. Because the number of CD34+ MV did not increase it would appear that the large increase in CD117+ MV was due to increase in common myeloid progenitors.
Antigen archiving and management by lymphatic endothelial cells. (INC1P.363)
Authors: Tamburini Beth , Burchill Matthew , Kedl Ross 
Published: January 2023

Abstract
Antigen derived from virus infections such as influenza and Vesicular Stomatitis Virus (VSV) can persist well beyond the natural rise and fall of the adaptive immune response against the infection. Antigen can similarly persist following both viral Vaccinia challenge and subunit vaccination. Surprisingly, persisting antigen from either Vaccinia or subunit vaccination is captured and maintained by a stromal cell subset: Lymphatic Endothelial Cells (LECs). The duration of antigen persistence is directly correlated with antigen dose and pattern recognition receptor (PRR) activation. PRR induced inflammation leads to LEC proliferation followed by antigen persistence in the lymph node. The coupling of LEC proliferation and antigen capture identifies a novel mechanism by which the secondary lymphoid stroma stores, or “archives”, antigens for extended periods of time after antigen challenge. Consistent with the idea that viral antigen persistence impacts the function of circulating memory T cells, we find that vaccine elicited antigen archiving on LECs has a significant impact on the fate of circulating memory T cells. As such, antigen archiving on LECs leads to increased production of interferon gamma and interleukin 2 by antigen specific CD8 T cells and protection against secondary infection. These findings may broadly impact our understanding of how lymph node stroma, specifically LECs, are involved in i) managing antigen and ii) protecting against re-infection.
Co-inhibitory factor induced NK cell exhaustion and immune escape meachanism in HBV-related hepatocellular carcinoma (INC1P.400)
Authors: sun cheng , Sun Rui , Tian Zhigang 
Published: January 2023

Abstract
The effectiveness of cancer immunotherapies targeting co-inhibitory molecules CTLA-4 and PD-1 have fully validated that reversal of tumor immune tolerance is an important new pathway for the treatment of tumor. Recent evidence shows that NK cell exhaustion in HBV related HCC patients. However, the underlying mechanism remains unclear. In our study, we found that the expression of NKG2A on NK cells from peripheral blood and different tissue regions of HCC was significantly increased, which then impaired NK cell-mediated cytotoxic capacity and interferon-γ production. We further found the same inhibition and exhaustion of NK cell in the different disease-progressing groups of HCC patients. Furthermore, we confirmed that IL-10 amounts in the immune microenvironment of hepatitis and HCC were highly related to the development of HCC. This study will help to understand the mechanism of immune tolerance of NK cells induced by HCC and verify the potential value of NKG2A as a novel intervention target for cancer immunotherapy.
Allergen-experienced ILC2s display memory-like functions and enhance type 2 lung inflammation (INC2P.410)
Authors: Martinez-Gonzalez Itziar , Mathä Laura , Takei Fumio 
Published: January 2023

Abstract
The ability of lymphocytes to remember their previous encounter with antigens and rapidly and vigorously respond to re-exposure to the same antigen is a key feature of the immune system. Whereas this immunological memory is thought to be antigen specific, here we show that group 2 innate lymphoid cells (ILC2s), which play a key role in type 2 immunity, display memory-like functions. Allergen-stimulated lung ILC2s rapidly proliferate and secrete cytokines that induce allergic lung inflammation, followed by a contraction phase, in which the inflammation is resolved. Some of the allergen-experienced ILC2s persist and vigorously react to an unrelated allergen, mediating a stronger allergic lung inflammation than naive ILC2s. Gene expression profiles of memory ILC2s are different from those of naive and effector ILC2s and display a gene signature of memory T cells. Antigen non-specific memory ILC2s may make individuals sensitive to a broad range of allergens.
Proteomic analysis of macrophages activated with salmonella lipopolysaccharide (INC2P.413)
Authors: makkar sarbjeet , Liyanage rohana , Lay Jackson , Narayan Rath 
Published: January 2023

Abstract
Macrophages play pivotal role in immunity. They are activated by pathogen derived molecules such as lipopolysaccharides (LPS) which triggers the production of various proteins that drive and resolve inflammation. There are many studies on the effect of LPS at the genome level but the knowledge of its proteomic effects is limited. To determine the proteomic effects of LPS, we used Stable Isotope Labelling of Amino acids in Cell culture (SILAC) with a chicken macrophage cell line HTC, stimulated with Salmonella typhimurium LPS. The heavy (H) (13C-lysine) labelled cells were treated with LPS and the regular or light lysine (L) grown cells treated as controls. After 16h of stimulation, the proteins were extracted, quantified, and an equal amount from both H and L cells mixed. The protein mixtures were subjected to reduction/alkylation, and trypsin digestion followed by high throughput liquid chromatography/ tandem mass spectrometry. We quantified 133 proteins using Skyline software, out of which 13 were upregulated and 11 down regulated. Some of the upregulated proteins included HSP 70 and 90, DNA helicases, prostaglandin D synthase and CCL5 ligand. The down regulated proteins were ubiquitin, proteasome, and proteins related to protease activity. In conclusion this study suggests that activation of macrophages with LPS results in differential expressions of proteins involved in cytoskeleton remodeling, cell migration and cell signaling pathways involved in immune response.