bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory T Cells Target Chemokine Secretion by Dendritic Cells Independently of Their Capacity To Regulate T Cell Proliferation
Authors: Morlacchi Sara , Dal Secco Valentina , Soldani Cristiana , Glaichenhaus Nicolas , Viola Antonella , Sarukhan Adelaida 
Published: May 2011

Abstract
The clinical manipulation of regulatory T cells (Tregs) represents a promising strategy for the regulation of unwanted immune responses. It is now becoming clear that Tregs exert multiple effects on different cell targets under particular conditions; however, the interplay between these different factors remains unclear. Using mouse Tregs of known Ag specificity, we report in this study two different levels of Treg-mediated suppression: one that targets T cell proliferation and one that targets dendritic cell-mediated proinflammatory chemokine (CCL3 and CCL4) production. These two effects can be dissociated, and whereas modulation of T cell proliferation depends on the strength of the antigenic stimulus, modulation of chemokine production by dendritic cells does not. We also provide evidence that the bystander effect of Tregs on immune responses observed in vivo may be in great part explained by a decrease in the recruitment of target T cells, and therefore in the magnitude of the response, rather than by a direct effect on their priming or proliferation. Overall, our results shed some light on the different aspects that need to be considered when attempting to modulate Tregs for clinical purposes.
IFN-γ Secreted by CD103+ Dendritic Cells Leads to IgG Generation in the Mesenteric Lymph Node in the Absence of Vitamin A
Authors: Chang Jae-Hoon , Cha Hye-Ran , Chang Sun-Young , Ko Hyun-Jeong , Seo Sang-Uk , Kweon Mi-Na 
Published: May 2011

Abstract
Although the induction mechanism of secretory IgA has been well studied, that of IgG in the mucosal compartments is not well understood. In this study, vitamin A deficiency was convincingly shown to be associated with increased IgG in serum and intestinal fluid. We found increased numbers of IgG-secreting B cells in the lamina propria of the small intestine and mesenteric lymph node (MLN) of vitamin A-deficient (VAD) mice. Of note, IFN-γ secreted by MLN dendritic cells (DCs) was significantly augmented in VAD mice, unlike control mice, and CD103+ DCs were the main subsets to secrete IFN-γ. The aberrant increase of IgG in VAD mice can be ascribable to IFN-γ, because IFN-γ−/− VAD mice have normal IgG levels and the addition of rIFN-γ increased IgG production by B cells cocultured with MLN DCs from IFN-γ−/− VAD mice. Oral feeding of antibiotics resulted in significant reduction of IgG in VAD mice, indicating a critical role for altered commensal bacteria for IgG class-switching recombination in the absence of vitamin A. Collectively, vitamin A deficiency provokes the generation of IFN-γ–secreting CD103+ DCs, which may be a critical regulator for IgG generation in the MLN.
Airway Epithelial MyD88 Restores Control of Pseudomonas aeruginosa Murine Infection via an IL-1–Dependent Pathway
Authors: Mijares Lilia A. , Wangdi Tamding , Sokol Caroline , Homer Robert , Medzhitov Ruslan , Kazmierczak Barbara I. 
Published: May 2011

Abstract
The opportunistic human pathogen Pseudomonas aeruginosa causes rapidly progressive and tissue-destructive infections, such as hospital-acquired and ventilator-associated pneumonias. Innate immune responses are critical in controlling P. aeruginosa in the mammalian lung, as demonstrated by the increased susceptibility of MyD88−/− mice to this pathogen. Experiments conducted using bone marrow chimeric mice demonstrated that radio-resistant cells participated in initiating MyD88-dependent innate immune responses to P. aeruginosa. In this study we used a novel transgenic mouse model to demonstrate that MyD88 expression by epithelial cells is sufficient to generate a rapid and protective innate immune response following intranasal infection with P. aeruginosa. MyD88 functions as an adaptor for many TLRs. However, mice in which multiple TLR pathways (e.g., TLR2/TLR4/TLR5) are blocked are not as compromised in their response to P. aeruginosa as mice lacking MyD88. We demonstrate that IL-1R signaling is an essential element of MyD88-dependent epithelial cell responses to P. aeruginosa infection.
Natural but Not Inducible Regulatory T Cells Require TNF-α Signaling for In Vivo Function
Authors: Housley William J. , Adams Catherine O. , Nichols Frank C. , Puddington Lynn , Lingenheld Elizabeth G. , Zhu Li , Rajan Thiruchandurai V. , Clark Robert B. 
Published: May 2011

Abstract
TNF-α has a multifunctional role in autoimmune diseases as reflected in the variable responses of different human diseases to anti–TNF-α therapy. Recent studies have suggested that TNF-α modulates autoimmunity partially via effects on regulatory T cells (Tregs) and that these effects are mediated through the type II TNFR (TNFR2). We have investigated the requirement for TNFR2-expression on murine natural Tregs (nTregs) and induced Tregs (iTregs) in mediating suppression of colitis. Surprisingly, we find that TNFR2-expression is required for both spleen- and thymus-derived nTreg-mediated suppression, but is not required for iTreg-mediated suppression. Abnormal TNFR2−/− nTreg function was not associated with an in vivo decrease in accumulation, stability, or expression of markers known to be relevant in Treg function. Because iTregs are generated in the presence of TGF-β, we investigated whether activation in the presence of TGF-β could overcome the functional defect in TNFR2−/− nTregs. Although preactivation alone did not restore suppressive function of nTregs, preactivation in the presence of TGF-β did. These results identify potentially critical differences in activation requirements for nTregs versus iTregs. Furthermore, our findings are consistent with reports suggesting that nTregs are activated in sites of inflammation while iTregs are activated in lymph nodes. Finally, by demonstrating that nTregs require TNF-α for optimal function whereas iTregs do not, our results suggest that the enigma of variable responses of different human diseases to anti–TNF-α therapy may relate to whether nTregs or iTregs have the predominant regulatory role in a given disease.
Invariant NKT Cells Producing IL-4 or IL-10, But Not IFN-γ, Inhibit the Th1 Response in Experimental Autoimmune Encephalomyelitis, Whereas None of These Cells Inhibits the Th17 Response
Authors: Oh Sae Jin , Chung Doo Hyun 
Published: May 2011

Abstract
Experimental autoimmune encephalomyelitis (EAE) is mediated by Th1 and Th17 cells. Invariant NKT (iNKT) cells prevent EAE in an IL-4–, IL-10–, and IFN-γ–dependent manner. However, which of the iNKT cell-produced cytokines regulates the Th1 or Th17 response in EAE remains unclear. Wild-type B6 and Jα18−/− mice were immunized with MOG35–55 peptide to address this issue. Clinical scores for EAE, IL-17, and IFN-γ transcript levels, and IL-17– or IFN-γ–expressing CD4+ T cell percentages in the CNS and draining lymph nodes were higher in Jα18−/− than in B6 mice, but all of these parameters in the CNS were reduced by the adoptive transfer of wild-type or IFN-γ–deficient iNKT cells into the Jα18−/− mice before immunization. In contrast, adoptive transfer of IL-4– or IL-10–deficient iNKT cells into Jα18−/− mice decreased IL-17 transcript levels and the percentage of IL-17–expressing CD4+ T cells in the CNS but did not affect clinical scores, IFN-γ transcript levels, or the percentage of IFN-γ–expressing CD4+ T cells in the CNS. Taken together, IL-4– and IL-10–producing iNKT cells inhibit the Th1 cell response, but not the Th17 cell response, although wild-type iNKT cells suppress both the Th1 and Th17 responses in the CNS during EAE. Moreover, IFN-γ–producing iNKT cells have a minimal role in the regulation of the Th1 and Th17 responses in EAE.
Cutting Edge: IL-15–Independent Maintenance of Mucosally Generated Memory CD8 T Cells
Authors: Verbist Katherine C. , Field Mary B. , Klonowski Kimberly D. 
Published: May 2011

Abstract
Effective vaccines against intracellular pathogens rely on the generation and maintenance of memory CD8 T cells (Tmem). Hitherto, evidence has indicated that CD8 Tmem use the common γ-chain cytokine IL-15 for their steady-state maintenance in the absence of Ag. This evidence, however, has been amassed predominantly from models of acute, systemic infections. Given that the route of infection can have significant impact on the quantity and quality of the resultant Tmem, reliance on limited models of infection may restrict our understanding of long-term CD8 Tmem survival. In this article, we show IL-15–independent generation, maintenance, and function of CD8 Tmem after respiratory infection with influenza virus. Importantly, we demonstrate that alternating between mucosal and systemic deliveries of the identical virus prompts this change in IL-15 dependence, necessitating a re-evaluation of the current model of CD8 Tmem maintenance.
Genetic Segregation of Inflammatory Lung Disease and Autoimmune Disease Severity in SHIP-1−/− Mice
Authors: Maxwell Mhairi J. , Duan Mubing , Armes Jane E. , Anderson Gary P. , Tarlinton David M. , Hibbs Margaret L. 
Published: May 2011

Abstract
Alternatively activated M2 macrophages are implicated as both regulators and agents of lung disease, but their control is poorly understood. SHIP-1 is a 5′ inositol phosphatase that negatively regulates the PI3K signaling pathway implicated in inflammation. SHIP-1–deficient mice have defects in hematopoiesis and B cell development, and die prematurely due to consolidation of lungs with M2-skewed macrophages. SHIP-1 is thought to restrain M2 macrophage polarization, with deregulated M2 skewing coinciding with severe lung disease in SHIP-1–deficient mice. To determine the influence of genetic background on the lung phenotype in SHIP-1−/− mice, we backcrossed the SHIP-1 null mutation onto C57BL/6 (Th2-resistant) and BALB/c (Th2-prone) backgrounds. Remarkably, we found that inflammatory lung disease was severe in C57.SHIP-1−/− mice, but absent in BALB.SHIP-1−/− mice. C57.SHIP-1−/−, but not BALB.SHIP-1−/− mice had greatly increased myeloid progenitors, myeloid hyperplasia, markedly enhanced numbers of activated alveolar macrophages, and elevated amounts of Th2 and proinflammatory cytokines in bronchoalveolar lavage fluid and serum, suggesting that deregulated cytokine production induced disease. C57.SHIP-1−/− mice also developed severe B cell-dependent autoimmune disease, which was markedly attenuated on the BALB/c background. These data demonstrate that, contrary to current concepts, loss of SHIP-1 alone is not sufficient to cause lung inflammation, with disease only manifest on a permissive genetic background. This finding questions the nature of the lung disease in SHIP-1−/− mice, suggesting that its M2 classification is not strictly correct. Future identification of disease-promoting loci might reveal determinants of comorbid lung disease and autoimmunity and uncover potentially useful therapeutic targets.
Activation of Endothelial Roundabout Receptor 4 Reduces the Severity of Virus-Induced Keratitis
Authors: Mulik Sachin , Sharma Shalini , Suryawanshi Amol , Veiga-Parga Tamara , Reddy Pradeep B. J. , Rajasagi Naveen K. , Rouse Barry T. 
Published: May 2011

Abstract
Antiangiogenic molecules exert a feedback control to restrain pathological angiogenesis, which includes physical binding or inhibition of angiogenic signaling in blood vessel endothelial cells. The latter is the case in which Slit2 ligand-dependent activation of the blood vessel endothelial cell receptor roundabout 4 (Robo4) occurs. In this study, we demonstrate that Robo4 receptors are upregulated following HSV infection of the eye on the majority of the new blood vessel endothelial cells that occur in the corneal stroma. However, expression levels of the ligand for Robo4 receptors, Slit2, was not significantly increased during the disease process, and the knockdown of Slit2 gene expression using lentiviral short hairpin RNAs had no effect on the extent of pathological angiogenesis. In contrast, providing additional Slit2 protein by subconjunctival administration resulted in significantly reduced angiogenesis. The Slit2 binding to Robo4 was shown to block the downstream vascular endothelial growth factor signaling molecules Arf 6 and Rac 1 and reduce the antiapoptotic molecule Bcl-xL in blood vessel endothelial cells. Our results indicate that augmenting the host Robo4/Slit2 system could provide a useful therapeutic approach to control pathological angiogenesis associated with HSV induced stromal keratitis.
Proteasomes, TAP, and Endoplasmic Reticulum-Associated Aminopeptidase Associated with Antigen Processing Control CD4+ Th Cell Responses by Regulating Indirect Presentation of MHC Class II-Restricted Cytoplasmic Antigens
Authors: Dragovic Srdjan M. , Hill Timothy , Christianson Gregory J. , Kim Sungjune , Elliott Tim , Scott Diane , Roopenian Derry C. , Van Kaer Luc , Joyce Sebastian 
Published: May 2011

Abstract
Cytoplasmic Ags derived from viruses, cytosolic bacteria, tumors, and allografts are presented to T cells by MHC class I or class II molecules. In the case of class II-restricted Ags, professional APCs acquire them during uptake of dead class II-negative cells and present them via a process called indirect presentation. It is generally assumed that the cytosolic Ag-processing machinery, which supplies peptides for presentation by class I molecules, plays very little role in indirect presentation of class II-restricted cytoplasmic Ags. Remarkably, upon testing this assumption, we found that proteasomes, TAP, and endoplasmic reticulum-associated aminopeptidase associated with Ag processing, but not tapasin, partially destroyed or removed cytoplasmic class II-restricted Ags, such that their inhibition or deficiency led to dramatically increased Th cell responses to allograft (HY) and microbial (Listeria monocytogenes) Ags, both of which are indirectly presented. This effect was neither due to enhanced endoplasmic reticulum-associated degradation nor competition for Ag between class I and class II molecules. From these findings, a novel model emerged in which the cytosolic Ag-processing machinery regulates the quantity of cytoplasmic peptides available for presentation by class II molecules and, hence, modulates Th cell responses.
Cutting Edge: The Membrane Attack Complex of Complement Is Required for the Development of Murine Experimental Cerebral Malaria
Authors: Ramos Theresa N. , Darley Meghan M. , Hu Xianzhen , Billker Oliver , Rayner Julian C. , Ahras Malika , Wohler Jillian E. , Barnum Scott R. 
Published: May 2011

Abstract
Cerebral malaria is the most severe complication of Plasmodium falciparum infection and accounts for a large number of malaria fatalities worldwide. Recent studies demonstrated that C5−/− mice are resistant to experimental cerebral malaria (ECM) and suggested that protection was due to loss of C5a-induced inflammation. Surprisingly, we observed that C5aR−/− mice were fully susceptible to disease, indicating that C5a is not required for ECM. C3aR−/− and C3aR−/− × C5aR−/− mice were equally susceptible to ECM as were wild-type mice, indicating that neither complement anaphylatoxin receptor is critical for ECM development. In contrast, C9 deposition in the brains of mice with ECM suggested an important role for the terminal complement pathway. Treatment with anti-C9 Ab significantly increased survival time and reduced mortality in ECM. Our data indicate that protection from ECM in C5−/− mice is mediated through inhibition of membrane attack complex formation and not through C5a-induced inflammation.
Genetic Variation Determines Mast Cell Functions in Experimental Asthma
Authors: Becker Marc , Reuter Sebastian , Friedrich Pamela , Doener Fatma , Michel Anastasija , Bopp Tobias , Klein Matthias , Schmitt Edgar , Schild Hansjörg , Radsak Markus P. , Echtenacher Bernd , Taube Christian , Stassen Michael 
Published: May 2011

Abstract
Mast cell-deficient mice are a key for investigating the function of mast cells in health and disease. Allergic airway disease induced as a Th2-type immune response in mice is employed as a model to unravel the mechanisms underlying inception and progression of human allergic asthma. Previous work done in mast cell-deficient mouse strains that otherwise typically mount Th1-dominated immune responses revealed contradictory results as to whether mast cells contribute to the development of airway hyperresponsiveness and airway inflammation. However, a major contribution of mast cells was shown using adjuvant-free protocols to achieve sensitization. The identification of a traceable genetic polymorphism closely linked to the KitW-sh allele allowed us to generate congenic mast cell-deficient mice on a Th2-prone BALB/c background, termed C.B6-KitW-sh. In accordance with the expectations, C.B6-KitW-sh mice do not develop IgE- and mast cell-dependent passive cutaneous anaphylaxis. Yet, unexpectedly, C.B6-KitW-sh mice develop full-blown airway inflammation, airway hyperresponsiveness, and mucus production despite the absence of mast cells. Thus, our findings demonstrate a major influence of genetic background on the contribution of mast cells in an important disease model and introduce a novel strain of mast cell-deficient mice.
Mixed Molybdenum–Tungsten Oxide as Dual‐Band, VIS–NIR Selective Electrochromic Material
Authors: Gillissen Florian , Lobet Michaël , Dewalque Jennifer , Colson Pierre , Spronck Gilles , Gouttebaron Rachel , Duttine Mathieu , Faceira Brandon , Rougier Aline , Henrard Luc , Cloots Rudi , Maho Anthony 
Published: February 2025

AbstractThe energy efficiency of smart windows can be greatly improved by integrating dual‐band electrochromic materials based on nanostructured doped metal oxides, as these allow for the dynamic and independent control of light and heat supplies in buildings, respectively, related to transmitted visible (VIS) and near‐infrared (NIR) solar radiations. Mixed molybdenum–tungsten oxides MoyW1−yO3−δ “MoWOx” are considered as innovative compounds in this context: in comparison with parent WO3−δ formulations, a remarkable increase of unpaired electrons can be obtained from the formation of a larger amount of both reduced species and oxygen vacancies during the synthetic process of MoWOx materials, with a consequently boosted intensity of light absorption by 850–900 nm wavelengths. Consecutively, spin‐coated films obtained from MoWOx structures, solvothermally synthesized for 1 h from 2/1 Mo/W atomic ratios, are shown to be electrochromically commutable through a noticeable VIS‐darkened and NIR‐transparent warm state, while WO3−δ benchmarks classically evolve between bright (VIS‐ and NIR‐bleached), cool (VIS‐bleached, NIR‐opaque), and dark (VIS‐ and NIR‐opaque) states. All in all, such advanced optical functionalities are of high interest for fine‐tuning the selectivity and improving the efficiency of electrochromic fenestration solutions, further improving their capacity to adapt to different climates, seasons, and user preferences.
An Algebraic Roadmap of Particle Theories Part II: Theoretical Checkpoints
Authors: Furey Nichol 
Published: February 2025

AbstractAn optimal algebraic framework of particle physics has a number of checkpoints to pass. As a minimum, models should conform to the Coleman‐Mandula theorem (or establish a loophole), evade familiar fermion doubling problems, naturally explain the Standard Model's chirality, exclude B‐L gauge symmetry at low energy, and explain the existence of three generations. The framework introduced in ref. [1] is shown to passes checkpoints , and has yet to cross . The discussion is concluded by elucidating an unexpected appearance of spacetime symmetries.
CTAB‐Assisted Hydrothermal Synthesis of CoFeMo Layered Double Hydroxides for Efficient Oxygen Evolution Reactions
Authors: Li Miao , Zhang Hao , Chen Ming , Wang Jing , Duan Jiachen , Ma Suzhe , Liang Kun , Ma Jiantai 
Published: February 2025

AbstractThe sluggish kinetics of the oxygen evolution reaction (OER), one of the half‐reactions in water electrolysis, severely constrains the large‐scale implementation of this technology. Therefore, identifying electrocatalysts with superior OER performance is of critical importance. In this study, a CTAB‐assisted hydrothermal method was employed to synthesize CoFeMo layered double hydroxide (LDH) nanosheets on nickel foam (NF) to achieve enhanced OER activity. The incorporation of Mo resulted in an increased number of active sites and improved electrical conductivity, yielding overpotentials of 164 and 265 mV at 10 and 50 mA cm−2, respectively surpassing the performance of both CoFe LDH/NF and RuO₂/NF, as well as most previously reported OER catalysts. The exceptional activity was attributed to the high valence state of Mo, which stabilizes neighboring metals through electronic structure modulation. In addition, the presence of the cationic surfactant CTAB during the hydrothermal process effectively suppressed metal agglomeration and regulated the morphology. Overall, this work demonstrates that CoFeMo LDH/NF synthesized via CTAB‐assisted hydrothermal methods serves as a highly effective electrocatalyst for oxygen evolution reactions.
A General Access to Aryl‐Alkyl Ketones via Nickel‐Catalyzed Carbonylative Reductive Cross‐Coupling Reactions
Authors: Su Lei , Gao Shen , Chen Lijuan , Yan Jie , Jiang Yuanli , Zheng Qingshu , Liu Jiawang 
Published: February 2025

AbstractTransition‐metal‐catalyzed carbonylation reactions have emerged as a versatile and powerful strategy for the production of diverse value‐added carbonyl‐containing compounds. Nevertheless, the carbonylative synthesis of alkyl ketones, particularly those incorporating secondary or tertiary alkyl fragments, remains underexplored and poses significant challenges. Herein, we present a nickel‐catalyzed carbonylative reductive cross‐coupling reaction to synthesize a wide range of aryl‐alkyl ketones from readily available alkyl halides, aryl iodides, and Mo(CO)6. This protocol exhibits excellent compatibility with primary, secondary, and tertiary alkyl electrophiles as well as aryl electrophiles bearing electron‐withdrawing or electron‐donating groups, offering a general access to aryl‐alkyl ketones under mild conditions. Mechanistic studies reveal that Mo(CO)6 not only serves as a safe and effective CO surrogate, but also plays a crucial role in facilitating the nickel carbonyl species, which is critical for promoting the selective synthesis of aryl‐alkyl ketones.