bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secreted M-Ficolin Anchors onto Monocyte Transmembrane G Protein-Coupled Receptor 43 and Cross Talks with Plasma C-Reactive Protein to Mediate Immune Signaling and Regulate Host Defense
Authors: Zhang Jing , Yang Lifeng , Ang Zhiwei , Yoong Sia Lee , Tran Thi Thu Thuy , Anand Ganesh Srinivasan , Tan Nguan Soon , Ho Bow , Ding Jeak Ling 
Published: October 2010

Abstract
Although transmembrane C-type lectins (CLs) are known to initiate immune signaling, the participation and mechanism of action of soluble CLs have remained enigmatic. In this study, we found that M-ficolin, a conserved soluble CL of monocyte origin, overcomes its lack of membrane-anchor domain by docking constitutively onto a monocyte transmembrane receptor, G protein-coupled receptor 43 (GPCR43), to form a pathogen sensor-cum-signal transducer. On encountering microbial invaders, the M-ficolin–GPCR43 complex activates the NF-κB cascade to upregulate IL-8 production. We showed that mild acidosis at the local site of infection induces conformational changes in the M-ficolin molecule, which provokes a strong interaction between the C-reactive protein (CRP) and the M-ficolin–GPCR43 complex. The collaboration among CRP–M-ficolin–GPCR43 under acidosis curtails IL-8 production thus preventing immune overactivation. Therefore, we propose that a soluble CL may become membrane-associated through interaction with a transmembrane protein, whereupon infection collaborates with other plasma protein to transduce the infection signal and regulate host defense. Our finding implies a possible mechanism whereby the host might expand its repertoire of immune recognition-cum-regulation tactics by promiscuous protein networking. Furthermore, our identification of the pH-sensitive interfaces of M-ficolin–CRP provides a powerful template for future design of potential immunomodulators.
NFAT5 Regulates T Lymphocyte Homeostasis and CD24-Dependent T Cell Expansion under Pathologic Hypernatremia
Authors: Berga-Bolaños Rosa , Drews-Elger Katherine , Aramburu Jose , López-Rodríguez Cristina 
Published: October 2010

Abstract
Immune cells rely on the transcription factor NFAT5 to adapt to hypertonic stress. The hypertonicity-dependent role of NFAT5 in T cells in vivo remains unclear because mouse models of NFAT5 deficiency have produced substantially different T cell phenotypes. In this study, we analyzed the T cell compartment in NFAT5-null and T cell-specific NFAT5 knockout mice. We found that NFAT5-null mice had constitutive, pronounced hypernatremia and suffered a severe immunodeficiency, with T cell lymphopenia, altered CD8 naive/memory homeostasis, and inability to reject allogeneic tumors. By contrast, T cell-specific NFAT5 knockout mice had normal plasma tonicity, rejected allogeneic tumors, and exhibited only a mild, low-penetrance memory bias in CD8 cells. Notably, when T cells from these mice were cultured ex vivo in hypernatremic media, they exhibited features found in NFAT5-null mice, with pronounced naive/memory imbalance and impaired homeostatic survival in response to IL-7, as well as a severe inhibition of their mitogen-induced proliferation. By analyzing surface receptors whose expression might be affected in NFAT5-deficient cells, we identified CD24 as a novel NFAT5 target induced by hypertonicity both in vitro and in vivo, and required to sustain T cell expansion under osmostress. NFAT5 bound to the Cd24 promoter in response to hypertonicity facilitated the local derepression of chromatin and enhanced the expression of CD24 mRNA and protein. Altogether, our results indicate that the systemic hypernatremia of NFAT5-null mice is a major contributor to their immunodeficiency, and highlight the role of NFAT5 and CD24 in the homeostasis of T cells under osmostress in vivo.
IL-17 Regulates Adipogenesis, Glucose Homeostasis, and Obesity
Authors: Zúñiga Luis A. , Shen Wen-Jun , Joyce-Shaikh Barbara , Pyatnova Ekaterina A. , Richards Andrew G. , Thom Colin , Andrade Sofia M. , Cua Daniel J. , Kraemer Fredric B. , Butcher Eugene C. 
Published: October 2010

Abstract
Inflammatory mediators have the potential to impact a surprising range of diseases, including obesity and its associated metabolic syndrome. In this paper, we show that the proinflammatory cytokine IL-17 inhibits adipogenesis, moderates adipose tissue (AT) accumulation, and regulates glucose metabolism in mice. IL-17 deficiency enhances diet-induced obesity in mice and accelerates AT accumulation even in mice fed a low-fat diet. In addition to potential systemic effects, IL-17 is expressed locally in AT by leukocytes, predominantly by γδ T cells. IL-17 suppresses adipocyte differentiation from mouse-derived 3T3-L1 preadipocytes in vitro, and inhibits expression of genes encoding proadipogenic transcription factors, adipokines, and molecules involved in lipid and glucose metabolism. IL-17 also acts on differentiated adipocytes, impairing glucose uptake, and young IL-17–deficient mice show enhanced glucose tolerance and insulin sensitivity. Our findings implicate IL-17 as a negative regulator of adipogenesis and glucose metabolism in mice, and show that it delays the development of obesity.
TIM-4, a Receptor for Phosphatidylserine, Controls Adaptive Immunity by Regulating the Removal of Antigen-Specific T Cells
Authors: Albacker Lee A. , Karisola Piia , Chang Ya-Jen , Umetsu Sarah E. , Zhou Meixia , Akbari Omid , Kobayashi Norimoto , Baumgarth Nicole , Freeman Gordon J. , Umetsu Dale T. , DeKruyff Rosemarie H. 
Published: October 2010

Abstract
Adaptive immunity is characterized by the expansion of an Ag-specific T cell population following Ag exposure. The precise mechanisms, however, that control the expansion and subsequent contraction in the number of Ag-specific T cells are not fully understood. We show that T cell/transmembrane, Ig, and mucin (TIM)-4, a receptor for phosphatidylserine, a marker of apoptotic cells, regulates adaptive immunity in part by mediating the removal of Ag-specific T cells during the contraction phase of the response. During Ag immunization or during infection with influenza A virus, blockade of TIM-4 on APCs increased the expansion of Ag-specific T cells, resulting in an increase in secondary immune responses. Conversely, overexpression of TIM-4 on APCs in transgenic mice reduced the number of Ag-specific T cells that remained after immunization, resulting in reduced secondary T cell responses. There was no change in the total number of cell divisions that T cells completed, no change in the per cell proliferative capacity of the remaining Ag-specific T cells, and no increase in the development of Ag-specific regulatory T cells in TIM-4 transgenic mice. Thus, TIM-4–expressing cells regulate adaptive immunity by mediating the removal of phosphatidylserine-expressing apoptotic, Ag-specific T cells, thereby controlling the number of Ag-specific T cells that remain after the clearance of Ag or infection.
LFA-1 and Mac-1 Define Characteristically Different Intralumenal Crawling and Emigration Patterns for Monocytes and Neutrophils In Situ
Authors: Sumagin Ronen , Prizant Hen , Lomakina Elena , Waugh Richard E. , Sarelius Ingrid H. 
Published: October 2010

AbstractTo exit blood vessels, most (∼80%) of the lumenally adhered monocytes and neutrophils crawl toward locations that support transmigration. Using intravital confocal microscopy of anesthetized mouse cremaster muscle, we separately examined the crawling and emigration patterns of monocytes and neutrophils in blood-perfused unstimulated or TNF-α–activated venules. Most of the interacting cells in microvessels are neutrophils; however, in unstimulated venules, a greater percentage of the total monocyte population is adherent compared with neutrophils (58.2 ± 6.1% versus 13.6 ± 0.9%, adhered/total interacting), and they crawl for significantly longer distances (147.3 ± 13.4 versus 61.8 ± 5.4 μm). Intriguingly, after TNF-α activation, monocytes crawled for significantly shorter distances (67.4 ± 9.6 μm), resembling neutrophil crawling. Using function-blocking Abs, we show that these different crawling patterns were due to CD11a/CD18 (LFA-1)- versus CD11b/CD18 (Mac-1)-mediated crawling. Blockade of either Mac-1 or LFA-1 revealed that both LFA-1 and Mac-1 contribute to monocyte crawling; however, the LFA-1–dependent crawling in unstimulated venules becomes Mac-1 dependent upon inflammation, likely due to increased expression of Mac-1. Mac-1 alone was responsible for neutrophil crawling in both unstimulated and TNF-α–activated venules. Consistent with the role of Mac-1 in crawling, Mac-1 block (compared with LFA-1) was also significantly more efficient in blocking TNF-α–induced extravasation of both monocytes and neutrophils in cremaster tissue and the peritoneal cavity. Thus, mechanisms underlying leukocyte crawling are important in regulating the inflammatory responses by regulating the numbers of leukocytes that transmigrate.
Differential Regulation of Caspase-1 Activation via NLRP3/NLRC4 Inflammasomes Mediated by Aerolysin and Type III Secretion System during Aeromonas veronii Infection
Authors: McCoy Andrea J. , Koizumi Yukiko , Higa Naomi , Suzuki Toshihiko 
Published: October 2010

Abstract
Aeromonas spp. are Gram-negative bacteria that cause serious infectious disease in humans. Such bacteria have been shown to induce apoptosis in infected macrophages, yet the host responses triggered by macrophage death are largely unknown. In this study, we demonstrate that the infection of mouse bone marrow-derived macrophages with Aeromonas veronii biotype sobria triggers activation of caspase-1 with the ensuing release of IL-1β and pyroptosis. Caspase-1 activation in response to A. veronii infection requires the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain and both the NLRP3 and NLRC4 inflammasomes. Furthermore, caspase-1 activation requires aerolysin and a functional type III secretion system in A. veronii. Aerolysin-inducing caspase-1 activation is mediated through the NLRP3 inflammasome, with aerolysin-mediated cell death being largely dependent on the NLRP3 inflammasome. In contrast, the type III secretion system activates both the NLRP3 and NLRC4 inflammasomes. Inflammasome-mediated caspase-1 activation is also involved in host defenses against systemic A veronii infection in mice. Our results indicated that multiple factors from both the bacteria and the host play a role in eliciting caspase-1 activation during A. veronii infection.
Cutting Edge: Adaptive Versus Innate Receptor Signals Selectively Control the Pool Sizes of Murine IFN-γ– or IL-17–Producing γδ T Cells upon Infection
Authors: Ribot Julie C. , Chaves-Ferreira Miguel , d’Orey Francisco , Wencker Mélanie , Gonçalves-Sousa Natacha , Decalf Jérémie , Simas João P. , Hayday Adrian C. , Silva-Santos Bruno 
Published: October 2010

Abstract
γδ T lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. Contributing to this is their responsiveness to pathogen products, either with or without the involvement of the TCR and its coreceptors. This study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γδ T cells. Thus, MyD88 deficiency severely impaired the response to malaria infection of CD27(−), IL-17A–producing γδ T cells, but not of IFN-γ–producing γδ cells. Instead, the latter compartment was severely contracted by ablating CD27, which synergizes with TCRγδ in the induction of antiapoptotic mediators and cell cycle-promoting genes in CD27(+), IFN-γ–secreting γδ T cells. Hence, innate versus adaptive receptors differentially control the peripheral pool sizes of discrete proinflammatory γδ T cell subsets during immune responses to infection.
IgG1 Is Pathogenic in Leishmania mexicana Infection
Authors: Chu Niansheng , Thomas Bolaji N. , Patel Supriya R. , Buxbaum Laurence U. 
Published: October 2010

Abstract
There are &gt;2 million new cases of leishmaniasis annually, and no effective vaccine has been developed to prevent infection. In murine infection, Leishmania mexicana, which lives intracellularly in host macrophages, has developed pathways to hijack host IgG to induce a suppressive IL-10 response through FcγRs, the cell-surface receptors for IgG. To guide vaccine development away from detrimental Ab responses, which can accompany attempts to induce cell-mediated immunity, it is crucial to know which isotypes of IgG are pathogenic in this infection. We found that IgG1 and IgG2a/c induce IL-10 from macrophages in vitro equally well but through different FcγR subtypes: IgG1 through FcγRIII and IgG2a/c through FcγRI primarily, but also through FcγRIII. In sharp contrast, mice lacking IgG1 develop earlier and stronger IgG2a/c, IgG3, and IgM responses to L. mexicana infection and yet are more resistant to the infection. Thus, IgG1, but not IgG2a/c or IgG3, is pathogenic in vivo, in agreement with prior studies indicating that FcγRIII is required for chronic disease. This calls into question the assumption that macrophages, which should secrete IL-10 in response to IgG1 and IgG2a/c immune complexes, are the most important source of IL-10 generated by IgG–FcγR engagement in L. mexicana infection. Further investigations are required to better determine the cell type responsible for this immunosuppressive FcγRIII-induced IL-10 pathway and whether IgG2a/c is protective.
Chlamydia-Specific CD4 T Cell Clones Control Chlamydia muridarum Replication in Epithelial Cells by Nitric Oxide-Dependent and -Independent Mechanisms
Authors: Jayarapu Krupakar , Kerr Micah , Ofner Susan , Johnson Raymond M. 
Published: October 2010

Abstract
Chlamydia trachomatis serovars D–K are sexually transmitted intracellular bacterial pathogens that replicate in epithelial cells lining the human reproductive tract. It is clear from knockout mice and T cell depletion studies using Chlamydia muridarum that MHC class II and CD4 T cells are critical for clearing bacteria from the murine genital tract. It is not clear how CD4 T cells interact with infected epithelial cells to mediate bacterial clearance in vivo. Previous work using an epithelial tumor cell line showed that a Chlamydia-specific CD4 T cell clone was able to inhibit C. muridarum replication in vitro via induction of epithelial NO production. We have previously shown that Chlamydia-specific CD4 T cell clones can recognize and be activated by infected reproductive tract epithelial cells and block Chlamydia replication in them. We extend those observations by investigating the mechanism used by a panel of CD4 T cell clones to control Chlamydia replication in epithelial cells. We found that Chlamydia-specific CD4 T cell clones were cytolytic, but that cytolysis was not likely critical for controlling C. muridarum replication. For one, CD4 T cell clone-induced epithelial NO production was critical for controlling replication; however, the most potent CD4 T cell clones were dependent on T cell degranulation for replication control with only a minor additional contribution from NO production. We discuss our data as they relate to existing knockout mouse studies addressing mechanisms of T cell-mediated control of Chlamydia replication and their implications for intracellular epithelial pathogens in mouse models.
Protective Endogenous Cyclic Adenosine 5′-Monophosphate Signaling Triggered by Pemphigus Autoantibodies
Authors: Spindler Volker , Vielmuth Franziska , Schmidt Enno , Rubenstein David S. , Waschke Jens 
Published: October 2010

Abstract
Pemphigus vulgaris (PV) is an autoimmune skin disease mediated by autoantibodies directed against the cadherin-type cell adhesion molecules desmoglein (Dsg) 3 and Dsg1 and is characterized by loss of keratinocyte cohesion and epidermal blistering. Several intracellular signaling pathways, such as p38MAPK activation and RhoA inhibition, have been demonstrated to be altered following autoantibody binding and to be causally involved in loss of keratinocyte cohesion. In this paper, we demonstrate that cAMP-mediated signaling completely prevented blister formation in a neonatal pemphigus mouse model. Furthermore, elevation of cellular cAMP levels by forskolin/rolipram or β receptor agonist isoproterenol blocked loss of intercellular adhesion, depletion of cellular Dsg3, and morphologic changes induced by Ab fractions of PV patients (PV-IgG) in cultured keratinocytes. Incubation with PV-IgG alone increased cAMP levels, indicating that cAMP elevation may be a cellular response pathway to strengthen intercellular adhesion. Our data furthermore demonstrate that this protective pathway may involve protein kinase A signaling because protein kinase A inhibition attenuated recovery from PV-IgG–induced cell dissociation. Finally, cAMP increase interfered with PV-IgG–induced signaling by preventing p38MAPK activation both in vitro and in vivo. Taken together, our data provide insights into the cellular response mechanisms following pemphigus autoantibody binding and point to a possible novel and more specific therapeutic approach in pemphigus.
Human Papillomavirus 16-Associated Cervical Intraepithelial Neoplasia in Humans Excludes CD8 T Cells from Dysplastic Epithelium
Authors: Trimble Cornelia L. , Clark Rachael A. , Thoburn Christopher , Hanson Nicole C. , Tassello Jodie , Frosina Denise , Kos Ferdynand , Teague Jessica , Jiang Ying , Barat Nicole C. , Jungbluth Achim A. 
Published: October 2010

AbstractHigh-grade cervical dysplasia caused by human papillomavirus (HPV) type 16 is a lesion that should be susceptible to an HPV-specific immune response; disease initiation and persistence is predicated on expression of two viral Ags, E6 and E7. In immune-competent subjects, at least 25% of HPV16+ high-grade cervical dysplasia lesions undergo complete regression. However, in the peripheral blood, naturally occurring IFN-γ T cell responses to HPV E6 and E7 are weak, requiring ex vivo sensitization to detect, and are not sufficiently sensitive to predict regression. In this study, we present immunologic data directly assessing cervical lymphocytes from this cohort. We found that nearly all cervical tissue T cells express the mucosal homing receptor, α4β7 surface integrin. T cells isolated from dysplastic mucosa were skewed toward a central memory phenotype compared with normal mucosal resident T cells, and dysplastic lesions expressed transcripts for CCL19 and CCL21, raising the possibility that the tissue itself sustains a response that is not detectable in the blood. Moreover, lesion regression in the study window could retrospectively be predicted at study entry by the ability of CD8+ T cells to gain access to lesional epithelium. Vascular endothelial expression of mucosal addressin cell adhesion molecule-1, the ligand that supports entry of α4β7+ T cells into tissues, colocalized tightly with the distribution of CD8 T cells and was not expressed in persistent dysplastic epithelium. These findings suggest that dysregulated expression of vascular adhesion molecules plays a role in immune evasion very early in the course of HPV disease.
Synthesis of Propiolic Acids via Copper‐Catalyzed Insertion of Carbon Dioxide into the CH Bond of Terminal Alkynes
Authors: Gooßen Lukas J. , Rodríguez Nuria , Manjolinho Filipe , Lange Paul P. 
Published: October 2010

AbstractA highly effective copper catalyst has been developed that promotes the insertion of carbon dioxide into the CH bond of terminal alkynes under unprecedentedly mild conditions. For the first time, propiolic acids can thus be synthesized in excellent yields from alkynes and carbon dioxide in the presence of the mild base cesium carbonate. The catalyst, (4,7‐diphenyl‐1,10‐phenanthroline)bis[tris(4‐fluorophenyl)phosphine]copper(I) nitrate, is easy accessible and relatively stable against air and water.
Dimethyl Sulfoxide/Potassium Hydroxide: A Superbase for the Transition Metal‐Free Preparation of Cross‐Coupling Products
Authors: Yuan Yu , Thomé Isabelle , Kim Seok Hwan , Chen Duanteng , Beyer Astrid , Bonnamour Julien , Zuidema Erik , Chang Sukbok , Bolm Carsten 
Published: October 2010

AbstractPotassium hydroxide (KOH) in dimethyl sulfoxide (DMSO) forms a superbasic medium that allows one to access cross‐coupling products from reactions between aryl halides with various sulfur‐, oxygen‐ and nitrogen‐based nucleophiles under transition metal‐free conditions.
Lack of respiratory improvement following remediation of a water‐damaged office building
Authors: Iossifova Yulia Y. , Cox‐Ganser Jean M. , Park Ju‐Hyeong , White Sandra K. , Kreiss Kathleen 
Published: October 2010

AbstractBackgroundDamp buildings are commonly remediated without removing employees or ongoing medical surveillance.MethodsWe examined paired pulmonary function and questionnaire data from 2002 and 2005 for 97 employees in a water‐damaged building during ongoing but incomplete remediation.ResultsWe observed no overall improvement in respiratory health, as reflected in symptom scores, overall medication use, spirometry abnormalities, or sick leave. Four employees went from borderline bronchial hyperresponsiveness to bronchial hyperresponsiveness; six developed abnormal spirometry; three more reported post‐occupancy current asthma, and four hypersensitivity pneumonitis. The number of participants without lower respiratory symptoms decreased from 27 in 2002 to 20 in 2005. Respiratory cases relocated in the building had a decrease in medication use and sick leave in 2005.ConclusionsDuring dampness remediation, relocation may be health protective and prevent incident building‐related respiratory cases. Without relocation of entire workforces, medical surveillance is advisable for secondary prevention of existing building‐related disease. Am. J. Ind. Med. 54:269–277, 2011. © 2010 Wiley‐Liss, Inc.
Risk of beryllium sensitization in a low‐exposed former nuclear weapons cohort from the cold war era
Authors: Mikulski Marek A. , Leonard Stephanie A. , Sanderson Wayne T. , Hartley Patrick G. , Sprince Nancy L. , Fuortes Laurence J. 
Published: October 2010

AbstractBackgroundThe nuclear weapons industry has long been known as a source of beryllium exposure.MethodsA total of 1,004 former workers from a nuclear weapons assembly site in the Midwest were screened for sensitization to beryllium (BeS). The screenings were part of the Department of Energy (DOE) Former Worker Program established in 1996.ResultsTwenty‐three (2.3%) workers were found sensitized to beryllium and this prevalence was comparable to other DOE sites. Occasional, direct exposure to beryllium through machining and grinding of copper–beryllium (Cu–Be) 2% alloy tools was found to increase the risk of sensitization compared to background exposure (OR = 3.83; 95% CI: 1.04–14.03) with a statistically significant trend (P = 0.03) revealing that particular jobs are associated with sensitization. Exposure potential in this study was estimated based on job titles and not personal exposure information.ConclusionsThese results confirm the need to screen workers using beryllium alloy tools in other industries and for consideration of altering work practices. Am. J. Ind. Med. 54:194–204, 2011. © 2010 Wiley‐Liss, Inc.