bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive humoral immune responses to type III capsular polysaccharide of Streptococcus pneumoniae.
Authors: Middleton Dustin Reed , Wantuch Paeton , Sun Lina , Avci Fikri Y 
Published: January 2023

Abstract
Capsular polysaccharides (CPSs) are important vaccine candidates given that they are located on the outermost surface of bacteria and have distinct structures. To induce CPS specific adaptive immune responses (i.e., T cell-mediated B cell responses), CPSs are conjugated with carrier proteins, to make glycoconjugate vaccines. The production of the current generation of glycoconjugate vaccines does not make use of specific scientific knowledge to maximize stimulation of critical immune cells (i.e., helper T cells) involved in producing protective IgG antibodies. Our previous discovery demonstrated that the mammalian CD4+ T cell repertoire contains a population of carbohydrate-specific T cells (i.e., Tcarbs) that recognize carbohydrate epitopes. Here, we investigate the interactions of carbohydrate epitopes with the key molecules of the adaptive immune system, MHCII proteins and T cell receptors (TCRs). This knowledge will have fundamental biological implications in our comprehension of how the adaptive immune system functions, and in future knowledge-based vaccine design. We employed a model bacterial polysaccharide antigen (capsular polysaccharide of type 3 Streptococcus pneumoniae, Pn3P) and its protein or peptide conjugates. We have collected evidence for the presence of a Tcarb repertoire that recognizes MHCII-presented Pn3P epitopes and drives Pn3P-specific IgG production by B cells. We have also generated Pn3 oligosaccharides through controlled depolymerization of Pn3P to be used in interation studies. Building on our expertise in these systems, we will define the MHCII and TCR interactions of processed Pn3P epitopes, and characterize immune responses that result from these interactions.
Characterization of the activation history and antigen specificity of B cells in meningeal clusters in Central Nervous System autoimmunity
Authors: Kerfoot Steven , Tesfagiorgis Yodit , Dang Amy K , Zhu Sarah , Craig Heather C 
Published: January 2023

Abstract
An important role for B cells in the pathology of Multiple Sclerosis (MS) is demonstrated by the therapeutic benefit of broad B cell depletion by anti-CD20 monoclonal antibodies. However, little is known about the subset(s) of B cells involved, the pathogenic mechanism(s), or the anatomical location from which they drive disease. Clusters of B cells have been observed in the meninges of some MS brains post mortem and it has been hypothesized that B cells drive pathology from these structures within the inflamed central nervous system (CNS). We used spontaneous and induced models of CNS autoimmune disease that incorporate B cell recognition of myelin autoantigen to investigate the identity and activation history of meningeal B cells in disease. B cells accumulated in the meninges in both models, often in clusters directly associated with demyelinating lesions. We found little evidence of organization into true lymphoid follicles nor evidence of typical B cell activation, despite clear ongoing inflammation and demyelination within the white matter. B cells had a largely naïve-like phenotype with little class-switch. Nevertheless, when compared to naïve lymph node B cells, these cells expressed more CD80 and less CD62L indicating some level of activation. To determine if meningeal B cells are specific for myelin antigen, we transferred fluorescent myelin-reactive T and B cells into wild-type recipient mice and induced EAE. While myelin reactive T cells dominated the T cell infiltrate of the spinal cord, as expected, almost no myelin reactive B cells were evident. This suggests that, unlike T cells, autoimmune B cells are excluded from the CNS in this model.
Autoantibody-mediated PAP in mice requires Myd88 in B cells
Authors: Ferretti Andrew P , Beedy Cady M , Barrington Robert A 
Published: January 2023

Abstract
Autoimmune pulmonary alveolar proteinosis (aPAP) is a lung syndrome caused by autoantibodies that neutralize granulocyte-macrophage colony-stimulating factor (GM-CSF, also known as Csf2). GM-CSF neutralization impairs alveolar macrophage function leading to the accumulation of surfactants in the alveoli. We recently discovered Rasgrp1-deficient mice (KO) are the first rodent model for this human disease, enabling the study of underlying immune mechanisms regulating the production of pathogenic GM-CSF-specific IgG autoantibodies. Because TLR signaling promotes breaks in B cell tolerance, and because GCs appear essential for autoantibody production in KO mice, we bred KO mice to mice conditionally lacking Myd88 in IgG1-expressing B cells (KO x Cγ1creMyd88fl/fl, referred to as KO Cγ1-Myd88) to test whether TLR signaling in mature B cells abrogates development of aPAP. As previously established, IgG1 was elevated in KO mice, and intriguingly KO Cγ1-Myd88 mice exhibited IgG1 titers similar to healthy control mice. Notably, GM-CSF-specific IgG serum autoantibody was also reduced in KO Cγ1-Myd88 mice in comparison to KO mice. Finally, histological analysis of H&E stained lung sections revealed that KO Cγ1-Myd88 mice do not develop aPAP. Taken together, this work has important implications for pathogenic anti-GM-CSF autoantibodies and aPAP, suggesting that 1) IgG1 is the predominant subclass and 2) TLR signaling in germinal centers is needed for break in tolerance of GM-CSF-specific B cells.
The expression of estrogen receptor alpha (ERα) by both the immune system and renal cells is required for induction of nephrotoxic serum-induced nephritis
Authors: Corradetti Chelsea , Madaio Michael , Caricchio Roberto 
Published: January 2023

Abstract
Glomerulonephritis (GN) is one of the most serious manifestations of systemic lupus erythematous (SLE). Lupus GN is characterized by severe inflammation and necrosis and it accounts for most morbidity and mortality. There is sex bias in SLE and estrogens may play an important role in GN susceptibility and progression. Interestingly, estrogen receptor alpha (ERα) in the renal tissue is highly expressed and the renal specific estrogen-induced gene activation is second only to that of reproductive organs. We have found that absence of estrogen receptor alpha protects female mice from developing nephritis, despite the presence of immune complexes in the kidneys and production of pro-inflammatory cytokines. To determine whether the ERα-expressing cells found in the immune system or kidney compartments were most important for inducing nephritis in this model. Bone marrow chimeras were generated from WT and ERαko mice and we used the nephrotoxic serum induced nephritis (NTN) model to induce GN. The results revealed that lack of ERα from both immune and renal cells was required to prevent disease in female mice; while males developed nephritis despite absence of ERα in either or both compartments. From these results, we conclude that ERα expression on immune and renal cells equally contribute to development of NTN and lack of ERα expression in both cell compartments is required to significantly reduce NTN in females.
Detection of anti-non bilayer phospholipids arragements antibodies and genotyping in patients with systemic lupus erythematosus and secondary antiphospholipid syndrome
Authors: Martínez María Teresa Hernández , Escamilla-Tilch Mónica , Reséndiz Albany , Wong-Baeza Carlos , Landa Carla , Jakez Juan , Barquera-Lozano Rodrigo , Hernández-Pando Rogelio , Granados Julio , Baeza Isabel 
Published: January 2023

Abstract
Phospholipids are the main structural constituents of all cell membranes, their form the smooth bilayer matrix that delimited cells in which membrane proteins are located. However, some anionic phospholipids can lead to the formation of nonbilayer phospholipid arrangements (NPA) within the bilayer. NPA are transient but when they are stabilized by the drugs chlorpromazine, procainamide or hydralazine, which produced lupus-like disease in humans, they induce a disease resembling human lupus in mice. Mice present IgM and IgG antibodies against NPA which appear 4 weeks before that autoantibodies against cardiolipin, histones, nuclear and lupus anticoagulant antibodies. Mice also present histopathological abnormalities in the skin and kidneys similar to those observed in systemic lupus erythematosus (SLE). We proposed that the recognition of NPA by anti-NPA antibodies and after by the classical complement pathway causes cell lysis exposing intracellular antigens with the consequent formation of autoantibodies. Antibodies against NPA have been described in patients with SLE, lepromatous leprosy and hypertensive disorders of pregnancy. The present investigation is a clinical study not randomized, prospective, in Mexican mestizos patients of any sex and age, with SLE or with secondary antiphospholipid syndrome in which we found that the elevated levels of anti-NPA antibodies could trigger autoimmunity in these diseases and we determined that high titers lead to increased activity and correlate with the expression of HLA-DR, HLA-DQ, HLA-A, HLA-B, IL-10 (-1082G/A, -819C/T, -592C/A) and PTPN22 (+1858C/T) alleles. All clinic assays were approved by the Committee of Bioethics of our Institutions.
The effect on transforming growth factor-beta-induced protein (beta ig-h3) expression by LPS and MDP stimulation to mice bone marrow derived macrophages
Authors: Kim Ha-Jeong , Rhe Su-Yeon , Nam Ju-Ok 
Published: January 2023

Abstract
The crosstalk between the inflammatory milieu and the immune response during inflammatory process is likely to be communicated in large part through the extracellular matrix (ECM). Transforming growth factor-beta-induced protein (beta ig-h3) is produced from several cells include fibroblasts, and exist extracellular matrix. big-h3 acts as a proinflammatory molecule. It is reported that blood concentration of big-h3 is high in CLP-induced septic mice, and the absence of big-h3 attenuated CLP-induced sepsis. MDP, is small peptide from Gram positive bacterial wall product peptidoglycan, is reported to suppress LPS induced immune response. Taken together, Here, we addressed how big-h3 is regulated by LPS and MDP costimulation in macrophages and what is its function on inflammatory site.
Differences in gene expression in human monocytes and macrophages from healthy and asthmatic donors in response to IL-4
Authors: Becerra-Diaz Mireya , McCormick Sarah M. , Fang Jessie Xi , Heller Nicola M 
Published: January 2023

Abstract
The lungs from asthmatics are in a state of Th2-driven inflammation with a shift in macrophage polarization toward an M2 profile induced by IL-4 and IL-13. The number of M2 macrophages in the lung correlates with asthma severity. Women have more lung M2 cells than men and are more likely to have asthma than men. We hypothesized that sex differences affect macrophage polarization in humans. First, we determined that M2-related gene expression was different between healthy and asthmatic donors in response to IL-4 and IL-13. Monocytes from asthmatics expressed more CCL17 in response to IL-4, while CCL22 and MMP12 expression was similar. We found that CD200R was highly expressed in response to IL-4 in monocyte derived-macrophages (MDM) from asthmatics compared with those of healthy donors. Furthermore, this increase was greater in MDM from women compared to men. Moreover, MMP12 and CCL22 expression were not different between the sexes. Interestingly, some genes (TGM2) were only up-regulated in MDM from asthmatics. Second, we analyzed the effect of male and female sex steroid hormones on the IL-4 signaling pathway. In the presence of IL-4, we found that both estrogen (E2) and dihydrotestosterone(active metabolite of testosterone) can induce changes in phosphorylation of Akt but not in STAT6 in MDM. Similar effects on signaling were results were obtained in U937, a human monocytic cell line. The stronger M2 response in female cells could be due to increased expression of estrogen receptors. We found that monocytes from women displayed greater expression of ERa isoforms. These results indicate a potential role for both intrinsic sex differences and E2 as inducers of M2 polarization in macrophages in asthma, leading to worse lung inflammation in women.
TGFβ inhibits IL-33-mediated mast cell activation in vitro and in vivo
Authors: Ndaw Victor S. , Kolawole Elizabeth Motunrayo , Abebayehu Daniel , Paez Patrick A , Baker Bianca , Barnstein Brian O , Taruselli Marcela T , Ryan John J 
Published: January 2023

Abstract
TGFβ is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGFβ suppresses IgE-mediated mast cell activation in human and mouse mast cells in vitro. IL-33 is a recently discovered member of the IL-1 family that functions as an “alarmin” stimulating mast cell responses and enhancing IgE-mediated activation. How TGFβ affects IL-33 signaling is now known. We find that mouse bone marrow-derived mast cells cultured in TGFβ -1, -2, or -3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13 and MCP-1, in a concentration-dependent manner. Furthermore, TGFβ also reduced expression of the IL-33 receptor ST2, as well as IL-33-mediated TAK1, IKB and ERK phosphorylation. TGF-β1 injection suppressed IL-33-mediated production of systemic inflammatory cytokines in vivo. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGFβ on IgE-mediated activation, demonstrate that TGFβ can provide broad and substantial inhibitory signals to activated mast cells. These data suggest possible therapeutic strategies to maintain mast cell homeostasis in autoimmune and allergic diseases.
A Novel, Quantitative, Multi-analyte Immunoassay to Detect Biomarkers Involved in Lung Disease
Authors: Anderson Michael 
Published: January 2023

Abstract
Lung disorders affect anywhere from 5–10% of the world’s population, and account for 1/6 of deaths worldwide. Pulmonary insult can arise from a multitude of factors, including those that are extrinsic, intrinsic, or iatrogenic-related. Manifestations of pulmonary disease include asthma, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), interstitial pneumonia (UIP), lung cancer, and tuberculosis (TB). The array of symptoms associated with these lung conditions involve shortness of breath, cough, fever, pleural effusion, pleural thickening pulmonary fibrosis, necrobiotic nodules, and bronchiolitis obliterans organizing pneumonia (BOOP). A decline in the quality of life in patients with lung disease is experienced not only physically, but also mentally due to the severity of the symptoms. One example is lung cancer, which is the most common cause of death in developed countries. Patients diagnosed with stage III or IV lung cancer have a survival rate of only 15% with current therapies.
The study presented here looked at several cytokine markers involved in airway constriction including IL-13, IL-5, and IL-4 as well as select biomarkers known to be involved in the regulatory pathways for IFN-g and TNF-a. The Simple Plexä assay that was employed is a novel, quantitative, multi-analyte immunoassay platform that delivers high precision and accuracy from only 25 μL of sample. This platform measures up to four analytes simultaneously from a single sample with very high sensitivity. It is a microfluidic-based system that allows parallel single analyte detection, and reduces non-specific antibody interactions often observed in other traditional multiplex platforms.
Leukocyte Intracellular Cytokine and Chemokine Response Kinetics to Poly-Trauma and Resuscitation in Non-Human Primates
Authors: Paredes Ruth Madelaine , Sooter Amanda , Vernon Philip Joseph , Glaser Jacob , Sheppard Forest 
Published: January 2023

Abstract

Background
Traumatic injury induces a significant inflammatory response. Post-injury responses of leukocyte subtypes, to include activation kinetics remain to be fully characterized to effectively direct therapeutic immunomodulation. We sought to determine leukocyte response kinetics to poly-trauma and resuscitation in non-human primates (NHPs).

Methods
Rhesus macaques (n=32) were randomized into four groups: 30min hemorrhagic shock (30HS), 60min HS (60HS), 60HS + laparotomy, and 60HS + laparotomy + femur fracture/repair followed by resuscitation and 24 hours monitoring. Blood was collected at baseline (BSLN), end of shock (EOS), end of resuscitation (EOR), t=360min and t=1440min and stained with a pan-leukocyte panel for flow cytometric analysis. Samples were stained for intracellular markers to differentiate leukocyte subsets such as cytotoxic lymphocytes (CTL), T helper (Th), Macrophage and B-cells. Results reported as mean±SEM, statistical analysis: two-way ANOVA with p&lt;0.05 significance.

Results
Levels of IL-10 in CTL, Th, B, NK-cells, and neutrophils increased over the experiment from BSLN. Hemorrhage induces a significant elevation of regulatory T-cells at 24hours, however, the addition of injuries abrogates this expansion. No other marker was found significantly different between groups/time points.

Conclusion
We have demonstrated that comprehensive flow analysis is effective for determining leukocyte subset kinetics in a poly-trauma model. Increases in T-cell IL-10 during resuscitation indicate nominal regulatory T-cell bursts. This was not observed in animals with additional injuries, suggesting animals with severe trauma may suffer from unfettered inflammatory complications downstream.
Disruption of Interleukin-17 receptor A (IL-17RA) gene in mice aggravates renal interstitial fibrosis in obstructive nephropathy
Authors: Ramani Kritika , Zhou Dong , Tan Roderick , Liu Youhua , Gaffen Sarah , Biswas Partha Sarathi 
Published: January 2023

Abstract
Renal fibrosis is the final outcome of obstructive nephropathy and a major cause of chronic renal failure. Renal fibrosis results from an imbalance between extracellular matrix (ECM) synthesis and degradation, which is regulated by multiple inflammatory mediators in the kidney. Recently, Interleukin-17 (IL-17) emerged as a key cytokine in lung and liver fibrosis. Although IL-17 producing cells were detected in the obstructed kidney, the role of IL-17 in renal fibrosis is unknown. We sought to define the contribution of IL-17 in renal fibrosis in obstructive nephropathy. Mice deficient in IL-17 receptor signaling (IL-17RA−/−) were assessed for renal fibrosis following unilateral ureteral obstruction (UUO), a well-characterized mouse model of obstructive nephropathy. We determined IL-17 receptor signaling is required for protection against renal fibrosis following UUO. IL-17RA−/− mice developed severe morphological injury and displayed increased deposition of collagen in the obstructed kidney compared to controls. We observed a significant decrease in the level of matrix degrading enzymes in the kidney of IL-17RA−/− mice, despite normal ECM synthesis, correlating with increased fibrosis. Overexpression of IL-17 increased the level of matrix degrading enzymes and protected mice from renal fibrosis. We also show that IL-17R signaling in tubular epithelial cells up regulated multiple genes of Kallikrein-kinin system, known to play a critical role in renal protection against kidney fibrosis. Our data clearly indicate a previously unappreciated role of IL-17 in renal protection against fibrosis. These results offer the opportunity for the development of potential therapies in the treatment of chronic kidney diseases.
The maternal IL-17a pathway in mice promotes autism-like phenotypes in offspring
Authors: Huh Jun R 
Published: January 2023

Abstract
Human studies suggest that maternal viral infection during pregnancy correlates with an increased frequency of Autism Spectrum Disorder (ASD) in the offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations involved in induction of ASD-like behavior in the MIA model have not been identified. Using both genetic mutants and blocking antibodies, here we show that RORgt-expressing T lymphocytes (e.g. Th17 cells) and the effector cytokine interleukin-17a (IL-17a) in mice are required in mothers for MIA-induced behavioral abnormalities in the offspring. We also find that MIA induces an abnormal cortical phenotype, which is dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of Th17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes.
Vitamin A deficiency disrupts conversion of inflammatory monocyte derived M2 macrophages into a tissue resident macrophage phenotype.
Authors: Gonzalez Michael A , Girgis Natasha , Gundra Uma Mahesh , Tang Mei San , Vozhilla Nikollaq , Loke Png 
Published: January 2023

Abstract
Alternatively activated M2 macrophages accumulate during inflammation from the recruitment of inflammatory monocytes, or through the proliferation of tissue resident macrophages. Monocyte derived and tissue resident M2 macrophages are phenotypically and functionally distinct, with UCP1 expression being a unique feature of tissue resident cells. We now show that monocyte derived M2 macrophages can acquire some of the phenotypic features of tissue resident cells after long-term residence in tissues. In liver granulomas of S. mansoni infected mice, UCP1 expression and proliferating cells accumulate in the periphery of mature granulomas. Genetic fate mapping macrophages derived from CX3CR1(+) monocytes indicate that UCP1 expressing cells are derived from monocyte precursors. Conversion to a tissue resident phenotype is independent of Stat6, although Stat6 regulates macrophage proliferation both intrinsically and extrinsically. Vitamin A deficiency (VAD) leads to dysregulation of the balance between monocyte and tissue macrophage derived M2 cells. Liver granulomas of S. mansoni infected VAD no longer express UCP1 and GATA6, indicating a failure to adopt tissue resident phenotype, and are associated with increased mortality. Inflammatory macrophages transferred into VAD mice fail to convert to a tissue resident phenotype. Genetic fate mapping experiments in VAD mice confirmed the failure of inflammatory macrophages to adopt tissue resident macrophage features despite long term tissue residence. Retinoic acid treatment of VAD mice reverses some of the defects. Hence, retinoic acid may regulate the conversion of monocyte derived inflammatory M2 macrophages into a tissue resident phenotype.