bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensifier les lieux du travail : Des temporalités de la scène au plateau
Authors: de Vaujany François-Xavier 
Published: January 2023

Historiquement ou plus métaphysiquement, l’unité spatiale et temporelle des modes d’organisation est aujourd’hui largement questionnée. La digitalisation, la pandémie, la crise climatique, un management plus décentré ou encore de multiples ruptures géopolitiques ont radicalement métamorphosé l’espace-temps du travail et son organisation. En s’inscrivant dans le vocabulaire et la logique du théâtre, cet essai propose de décrire à la fois un glissement et une tension générative entre la scène et la salle, puis la scène et le plateau. Si la scène est un lieu au sens le plus habituel, un emplacement bien défini et clos dans l’espace plus large du monde, le plateau est tout entier événements saisis dans la même durée et producteurs de lieux éphémères selon leur propre topologie. Plus que jamais décentrés, événementialisés et enjeux de profondeur, les lieux du management doivent aujourd’hui être intensifiés, démultipliés et mis en conversation. Gérés comme des plateaux, ils sont désormais abordés comme des expériences. Aux « spect-acteurs » managers de construire activement les co-présences ou les intensités pouvant placer leurs équipes dans des lieux communs souvent transitoires. Dans un contexte de généralisation du télétravail, ces intensifications des lieux sont plus que jamais nécessaires.
Immunometabolic Analysis of Synovial Fluid from Juvenile Idiopathic Arthritis Patients
Authors: Giacalone Vincent D , Cammarata-Mouchtouris Alexandre , Moncada-Giraldo Diego , Shenoy Sreekala P V , Ponder Lori A , Gergely Talia R , Kim Susan O , Chandler Joshua D , Vega-Fernandez Patricia , Manos Cynthia K , Flanagan Elaine R , Prahalad Sampath , Tirouvanziam Rabindra 
Published: January 2023

Abstract
Juvenile idiopathic arthritis (JIA) is an inflammatory rheumatic disorder. Polymorphonuclear neutrophils (PMNs) are present in JIA synovial fluid (SF), but with variable frequency. SF PMNs in JIA were previously shown to display high exocytic but low phagocytic and immunoregulatory activities. To further assess whether the degree of SF neutrophilia associated with altered immune responses in JIA, we collected SF and blood from 16 adolescent JIA patients. SF and blood leukocytes were analyzed by flow cytometry. SF and plasma were used for immune mediator quantification and metabolomics. Healthy donor blood T cells were cultured in SF to evaluate its immunoregulatory activities. PMN and T cell frequencies were bimodal in JIA SF, delineating PMN high/T cell low (PMNHigh) and PMN low/T cell high (PMNLow) samples. Proinflammatory mediators were increased in SF compared with plasma across patients, and pro- and anti-inflammatory mediators were further elevated in PMNHigh SF. Compared to blood, SF PMNs showed increased exocytosis and programmed death-1/programmed death ligand-1 expression, and SF PMNs and monocytes/macrophages had increased surface-bound arginase-1. SPADE analysis revealed SF monocyte/macrophage subpopulations coexpressing programmed death-1 and programmed death ligand-1, with higher expression in PMNHigh SF. Healthy donor T cells showed reduced coreceptor expression when stimulated in PMNHigh versus PMNLow SF. However, amino acid metabolites related to the arginase-1 and IDO-1 pathways did not differ between the two groups. Hence, PMN predominance in the SF of a subset of JIA patients is associated with elevated immune mediator concentration and may alter SF monocyte/macrophage phenotype and T cell activation, without altering immunoregulatory amino acids.
Inflammatory Chemokine Receptors Support Inflammatory Macrophage and Dendritic Cell Maturation
Authors: Bartolini Robin , Medina-Ruiz Laura , Hayes Alan J , Kelly Christopher J , Halawa Heba A , Graham Gerard J 
Published: January 2023

Abstract
Dendritic cells form clusters in vivo, but the mechanism behind this has not been determined. In this article, we demonstrate that monocytes from mice deficient in the chemokine receptors CCR1, CCR2, CCR3, and CCR5 display reduced clustering in vitro, which is associated with impaired dendritic cell and macrophage differentiation. We further show that the differentiating cells themselves produce ligands for these receptors that function, in a redundant manner, to regulate cell clustering. Deletion of, or pharmacological blockade of, more than one of these receptors is required to impair clustering and differentiation. Our data show that chemokines and their receptors support clustering by increasing expression of, and activating, cell-surface integrins, which are associated with cell–cell interactions and, in the context of monocyte differentiation, with reduced expression of Foxp1, a known transcriptional suppressor of monocyte differentiation. Our data therefore provide a mechanism whereby chemokines and their receptors typically found in inflammatory environments can interact to promote murine monocyte differentiation to macrophages and dendritic cells.
Current Status of Immunology Education in U.S. Medical Schools
Authors: Reynolds Austin B , Bhattacharjee Ritvik , Zhao Yuan 
Published: January 2023

Abstract
Immunology is an integral component of undergraduate medical education because of its critical role in many disease processes. Due to the complexity of the subject, the best practice of immunology education in the undergraduate medical curriculum has not been extensively discussed. This study intended to determine the current status of immunology education in U.S. medical schools with the hope of providing insight into curriculum design pertaining to this subject. Immunology curriculum information was collected from the curriculum Web pages of 199 U.S. medical schools, including multiple campuses. Data pertaining to the setting of immunology education such as subjects that are co-taught with immunology, timing of courses, credit hours, and integration level were recorded in Microsoft Excel for analysis. Of 199 U.S. medical schools studied, 174 posted curriculum information related to immunology online. For course settings, 59 (33.9%) offer immunology with microbiology, 42 (24.1%) offer immunology as part of a foundational sciences course, and 18 (10.3%) offer immunology as a stand-alone course. Ten programs (5.7%) have immunology fully integrated in system-based curriculum. Of 119 medical schools that provide information regarding timing, 94 (71.9%) provide immunology education in year 1 of the curriculum, 16 (9.2%) in year 2, and 9 (5.2%) in both years 1 and 2. Differences exist in allopathic versus osteopathic programs in the immunology curriculum setting. Credit hour data were not complete due to inconsistent availability. Our data suggest that immunology education in U.S. medical schools lacks consensus. Continued discussion on best practices of immunology education across U.S. medical schools is recommended.
Differential expression of complement receptors on human basophils and mast cells. Evidence for mast cell heterogeneity and CD88/C5aR expression on skin mast cells.
Authors: Füreder W , Agis H , Willheim M , Bankl H C , Maier U , Kishi K , Müller M R , Czerwenka K , Radaszkiewicz T , Butterfield J H , Klappacher G W , Sperr W R , Oppermann M , Lechner K , Valent P 
Published: January 2023

Abstract
Complement-dependent activation of immune cells is regulated by cell surface membrane receptors. In this study, expression of complement receptors (CR) on human blood basophils (n = 11), tissue mast cells (lung, n = 7; skin, n = 10; uterus, n = 4; tonsil, n = 3; heart, n = 10), and on respective human cell lines (basophil line KU-812, mast cell line HMC-1) was analyzed by the use of mAbs and indirect immunofluorescence. Normal blood basophils and KU-812 cells were found to express C5aR (CD88), membrane cofactor protein (CD46), decay-accelerating factor (CD55), and membrane attack complex inhibitory factor (CD59), as well as the previously recognized CR1 (CD35), CR3 alpha (CD11b), CR4 alpha (CD11c), and CR3/4 beta (CD18). Mast cells from all organs as well as HMC-1 cells expressed CD46, CD55, and CD59, but not CD11b, CD21, or CD35. The C5aR (CD88) was detectable on skin mast cells, a subset (5 to 15%) of cardiac mast cells, and on HMC-1 cells, but not on lung, uterus, or tonsillar mast cells (&lt; 5%). Moreover, double immunoperoxidase staining (tryptase vs C5aR/CD88) revealed in situ expression of C5aR on skin, but not lung mast cells. Recombinant human (rh) C5a, at 10(-10) to 10(-7) M, induced secretion of histamine from basophils (rhC5a, 10(-8) M: 53.4 +/- 3.1% vs control &lt; 5%) and from skin mast cells (rhC5a, 10(-8) M: 25.8 +/- 16.1% vs control &lt; 10% histamine release), but not from other mast cells (rhC5a or control: &lt; 10%, p &gt; 0.05). The rhC5a-induced secretion of histamine from basophils and skin mast cells was inhibited by S5/1, a blocking Ab against CD88 (basophils: 37.2% to 75.1%; skin mast cells: 39.2% to 83.9% inhibition, p &lt; 0.05). Together, this study shows that a) basophils and mast cells express a different profile of complement receptors, b) C5a-dependent mediator release in skin mast cells and basophils is mediated via CD88, and c) mast cells constitute a heterogeneous lineage in terms of expression of the C5a binding site CD88.
IL-13 and IL-4 inhibit bone resorption by suppressing cyclooxygenase-2-dependent prostaglandin synthesis in osteoblasts.
Authors: Onoe Y , Miyaura C , Kaminakayashiki T , Nagai Y , Noguchi K , Chen Q R , Seo H , Ohta H , Nozawa S , Kudo I , Suda T 
Published: January 2023

Abstract
Activated T cells secrete the cytokine IL-13, which regulates inflammatory and immune responses. To explore the role of IL-13 in bone metabolism, we examined the effects of the cytokine on bone resorption and PG synthesis in osteoblasts. IL-13 suppressed the bone-resorbing activity stimulated by IL-1 alpha, which was determined by the release of 45Ca from prelabeled mouse long bones. Histologic examinations revealed that IL-1 alpha markedly stimulated bone resorption with increased osteoclast recruitment, and that the simultaneous addition of IL-13 considerably inhibited it. The gamma-chain of IL-2 receptors may be functionally involved in the signal transduction of not only IL-2, but also IL-4, IL-7, and IL-13. Of these cytokines, IL-4 similarly suppressed IL-1 alpha-induced bone resorption, but IL-2 and IL-7 did not. Both IL-13 and IL-4 inhibited PGE2 production stimulated by IL-1 alpha in long bone cultures. Suppression of IL-1 alpha-induced bone resorption by IL-13 and IL-4 was recovered by adding exogenous PGE2 to the long bone cultures. Neither IL-4 nor IL-13 further inhibited IL-1 alpha-induced bone resorption in the presence of indomethacin. To examine the effects of IL-13 on PG synthesis, we measured the mRNA levels of cytosolic phospholipase A2 (cPLA2), constitutively expressed cyclooxygenase (COX-1) and inducible COX (COX-2) in mouse osteoblast-like cells. IL-1 alpha markedly stimulated the mRNA expression of COX-2, but not that of COX-1. Both IL-13 and IL-4 dose-dependently suppressed the IL-1 alpha-induced stimulation of both COX-2 mRNA expression and PGE2 synthesis. A small increase (1.7-fold) in cPLA2 mRNA levels was detected in the cultures with IL-1 alpha, but the expression was not affected by IL-13 or IL-4. These results indicated that IL-13 and IL-4 inhibit bone resorption by suppressing COX-2-dependent PG synthesis in osteoblasts.
Chemokines and T lymphocyte activation: II. Facilitation of human T cell trafficking in severe combined immunodeficiency mice.
Authors: Murphy W J , Tian Z G , Asai O , Funakoshi S , Rotter P , Henry M , Strieter R M , Kunkel S L , Longo D L , Taub D D 
Published: January 2023

Abstract
Previous studies from this laboratory have demonstrated that the chemokines RANTES (recombinant human regulated upon activation, normally T cell expressed and presumably secreted), macrophage chemotactic peptide-1, recombinant human macrophage inflammatory protein-1 alpha (rhMIP-1 alpha) IL-8, and IP-10 are capable of inducing human T cell infiltration into the injection site of severe combined immunodeficiency (SCID) mice reconstituted with human PBL. However, the ability of these chemokines to facilitate T cell homing into various lymphoid tissues has not been examined. Initial studies focused on the ability of rhMIP-1 beta to induce human T cell infiltration into injection sites in human PBL-SCID mice. SCID mice received s.c. injections of rhMIP-1 beta or PBS (1 microgram/injection) in the hindflank for 4 h or sequential injections for 3 days. Biopsies of the MIP-1 beta injection site revealed the presence of significant mononuclear cell accumulation 72 h after injection. Immunohistologic evaluation determined that significant numbers of human CD3+ T cells were recruited in response to MIP-1 beta injections, and this infiltration could be specifically blocked by co-administration of anti-MIP-1 beta antiserum. We subsequently examined these chemokine-injected mice for the effect of trafficking of human T cells to peripheral lymphoid organs. Flow cytometric analysis of the thymus in human PBL-SCID mice revealed that treatment with rhMIP-1 beta or rhRANTES, but not platelet factor-4, resulted in improved thymic homing of the human T cells after 72 h. This trafficking effect was shown to be direct, as pretreatment of the human T cells with the chemokines in vitro also improved peripheral lymphoid trafficking of the human cells. In addition, co-injection of rhMIP-1 beta with anti-1 beta antiserum abrogated the increase in T cell homing to the thymus. These data demonstrate that MIP-1 beta and RANTES directly augment human T cell trafficking to peripheral murine lymphoid tissues. Chemokines may, therefore, under either isogeneic or xenogeneic conditions, play a role in normal lymphocyte recirculation and homing, and may be of potential clinical use in promoting immune cell trafficking and function.
IL-15 promotes cytokine production of human T helper cells.
Authors: Mori A , Suko M , Kaminuma O , Inoue S , Ohmura T , Nishizaki Y , Nagahori T , Asakura Y , Hoshino A , Okumura Y , Sato G , Ito K , Okudaira H 
Published: January 2023

Abstract
IL-15 is a newly identified cytokine that has T cell and B cell growth factor activity similar to that of IL-2. In this study, a novel biologic function of IL-15 to promote cytokine production by human Th cells has been elucidated. Dermatophagoides farinae 11 (a major allergen of house dust mite)-specific human T cell clones produced IL-5 in response to recombinant human IL-15 as well as to either anti-CD3 or IL-2 stimulation. IL-5 mRNA became detectable 3 h after IL-15 stimulation and reached a maximum at 9 h. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was clearly transcribed in response to IL-15, indicating that the approximately 500-bp human IL-5 promoter/enhancer segment 5' upstream of the coding region sufficiently responded to IL-15. IL-15-induced IL-5 synthesis was completely inhibited by the tyrosine kinase inhibitor, herbimycin A, suggesting the involvement of tyrosine kinases in the signal transduction leading to IL-5 synthesis as well as to proliferation of T cells induced by IL-15. Whereas IL-5 production by human peripheral T cells was abolished by the addition of anti-IL-2-neutralizing Abs into the culture, IL-15 restored the IL-5 synthesis despite effective IL-2 neutralization. IL-15 produced at the site of allergic inflammation may play a role in the recruitment and activation of eosinophils by inducing IL-5 (a Th2 cytokine) production by T cells.
Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.
Authors: Moriyama H , Yokono K , Amano K , Nagata M , Hasegawa Y , Okamoto N , Tsukamoto K , Miki M , Yoneda R , Yagi N , Tominaga Y , Kikutani H , Hioki K , Okumura K , Yagita H , Kasuga M 
Published: January 2023

Abstract
The present study demonstrated that a short-term administration of mAbs against leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) at critical periods resulted in complete protection of autoimmune diabetes in non-obese diabetic (NOD) mice. When these mAbs were administered for only 6 days at 2 wk of age, neither diabetes nor insulitis was observed at 30 wk of age. It appears that the tolerance against beta cell Ag(s) was induced by this transient blockade of the LFA-1/ICAM-1 pathway. Protective suppressor activity was not enough to prevent diabetes because co-transfer of splenocytes from female NOD mice, which had received these mAbs at 2 wk of age, resulted in only a short delay of the diabetic onset caused by adoptive transfer of splenocytes from acutely diabetic NOD mice. Transfer of these splenocytes to young NOD mice could not also abrogate the spontaneous diabetes and insulitis. Furthermore, cyclophosphamide treatment could not abrogate the protection. When splenocytes from the treated NOD mice were transferred to NOD-SCID mice, none of the recipient mice developed significant insulitis and subsequent overt diabetes, suggesting the absence or the inactivation of diabetogenic effector T cells. However, splenic T cells from the insulitis-free NOD mice that had received the mAb treatment preserved proliferative responses to both islet cells and 65-kDa glutamic acid decarboxylase (GAD65) in vitro. These results suggest that a unique peripheral tolerance was induced by the transient blockade of the LFA-1/ICAM-1 pathway in an early age of NOD mice.
Expression of vascular cell adhesion molecule-1 by vascular endothelial cells in immune and nonimmune inflammatory reactions in the skin.
Authors: Harrison A A , Stocker C J , Chapman P T , Tsang Y T , Huehns T Y , Gundel R H , Peters A M , Davies K A , George A J , Robinson M K , Haskard D O 
Published: January 2023

Abstract
Expression of VCAM-1 was compared with that of E-selectin in cytokine-induced lesions and in delayed-type hypersensitivity reactions to tuberculin purified protein derivative (PPD) in pig skin. Lumenally expressed Ags were quantified by measuring localization in skin of i.v. injected (111)In-mAb 10.2C7 (anti-vascular cell adhesion molecule-1 (anti-VCAM-1), (125)I-mAb 1.2B6 (anti-E-selectin), and (99m)Tc-MOPC21 (control IgG1). Anti-VCAM-1 mAb uptake was greater following intradermal (i.d.) injection of TNF-alpha than following injection of IL-1, while the two cytokines induced similar uptake of anti-E-selectin. In immunologically naive pigs there was no detectable increase in anti-VCAM-1 after i.d. injection of PPD, although anti-E-selectin uptake was increased at 3 and 6 h. In contrast, i.d. injection of PPD in sensitized pigs led to increased uptake of both anti-VCAM-1 and anti-E-selectin at 6, 8, 24, and 48 h, each of which was significantly greater than the uptake of control IgG1 into the same lesions (each p &lt; 0.01). Anti-TNF-alpha mAb abolished the increased uptake of anti-VCAM-1 3 and 8 h following i.d. injection of PPD in sensitized pigs and significantly inhibited uptake at 24 h (p = 0.0025), but did not significantly reduce uptake of anti-E-selectin. We conclude that in this delayed-type hypersensitivity model 1) E-selectin expression by endothelial cells follows sequential Ag nonspecific and immune-specific phases, 2) increased VCAM-1 expression by endothelial cells is only seen in sensitized animals, and 3) expression of VCAM-1 appears to be relatively more dependent on TNF-alpha than E-selectin. Differential expression of E-selectin and VCAM-1 may influence the leukocytic infiltrate during the course of nonspecific and immune-specific inflammatory reactions.
mTOR regulates protection against lethal H5N1 influenza infection by modulating the antibody response (VAC2P.926)
Authors: McGargill Maureen , Keating Rachael , Hertz Tomer , Wehenkel Marie , Harris Tarsha , Edwards Benjamin , McClaren Jennifer , Brown Scott , Surman Sherri , Wilson Zachary , Bradley Philip , Hurwitz Julia , Chi Hongbo , Doherty Peter , Thomas Paul 
Published: January 2023

Abstract
Highly pathogenic H5N1 avian influenza viruses pose a continuing global threat. Current vaccines will not protect against novel pandemic viruses. Creating “universal” vaccines has been unsuccessful because the immunological mechanisms promoting heterosubtypic immunity are incompletely defined. We show that rapamycin, an immunosuppressive drug that inhibits mTOR, promotes cross-strain protection against a lethal H5N1 infection when administered during H3N2 virus immunization. Rapamycin reduced germinal center formation and inhibited B cell class-switching, yielding a unique repertoire of antibodies that mediated heterosubtypic protection. Our data establish a requirement for mTORC1 in B cell class-switching and demonstrate that rapamycin skews the antibody response away from high affinity variant epitopes, targeting more conserved elements of hemagglutinin. Our current data indicate that a primary intranasal infection with FluMist enhances heterosubtypic immunity even more, which can be further enhanced with rapamycin. In this model the CD8 T cells contribute to enhanced protection providing us a model to study the synergy between cross-reactive antibodies and CD8 T cells. These findings have intriguing implications for influenza vaccine design.
Gene-associated retinoid-interferon-induced mortality 19 (GRIM-19) attenuates autoimmune arthritis by regulation of Th17 and Treg cells (VAC3P.957)
Authors: Moon Young-Mee , Lee Jennifer , Lee Seon-Yeong , Kim Eun-Kyoung , Son Hea-Jin , Seo Hyeon Beom , Kwok Seung-Ki , Ju Ji Hyeon , Yang Chul-Woo , Park Sung-Hwan , Cho Mi-La 
Published: January 2023

Abstract
Signal transducer and activator of transcription 3 (STAT3) is a key transcriptional factor in interleukin (IL)-6-mediated Th17 differentiation. Because Th17 is believed to be a central player in rheumatoid arthritis (RA), we hypothesized that an endogenous STAT3 inhibitor, genes associated with retinoid-interferon-induced mortality 19 (GRIM-19), could attenuate collagen-induced arthritis (CIA) by suppressing Th17 and reciprocally increasing Treg. The numbers of CD4+/IL-17+ cells and CD4+ phosphorylated (p)-STAT3+ cells were decreased, while the numbers of CD4+/CD25+/Foxp3+ cells and CD4+/pSTAT5+ cells were increased in both GRIM-19 overexpression vector-administered and GRIM-19 Tg mice. Administration of GRIM-19 overexpression vector into CIA mice markedly suppressed the clinical and histological signs of arthritic joints. Similarly, when CIA was induced in GRIM-19 Tg mice, the arthritic phenotype was markedly attenuated and the expressions of inflammatory cytokines (IL-1β, IL-6, tumor necrosis factor-α, and IL-17) in arthritic joints were also significantly reduced. Moreover, bone marrow-derived monocytes/macrophages obtained from GRIM-19 Tg mice showed attenuated receptor activator of nuclear factor kappa-B ligand-induced osteoclastogenesis in vitro. GRIM-19 improved the clinical and histologic features of CIA and also inhibited osteoclast formation. These data suggest that GRIM-19 may be a novel treatment agent for RA.