bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory Effects of Surfactant Protein A on Surfactant Phospholipid Hydrolysis by Secreted Phospholipases A2
Authors: Chabot Sophie , Koumanov Kamen , Lambeau Gérard , Gelb Michael H. , Balloy Viviane , Chignard Michel , Whitsett Jeffrey A. , Touqui Lhousseine 
Published: April 2014

Abstract
Hydrolysis of surfactant phospholipids by secreted phospholipases A2 (sPLA2) contributes to surfactant dysfunction in acute respiratory distress syndrome. The present study demonstrates that sPLA2-IIA, sPLA2-V, and sPLA2-X efficiently hydrolyze surfactant phospholipids in vitro. In contrast, sPLA2-IIC, -IID, -IIE, and -IIF have no effect. Since purified surfactant protein A (SP-A) has been shown to inhibit sPLA2-IIA activity, we investigated the in vitro effect of SP-A on the other active sPLA2 and the consequences of sPLA2-IIA inhibition by SP-A on surfactant phospholipid hydrolysis. SP-A inhibits sPLA2-X activity, but fails to interfere with that of sPLA2-V. Moreover, in vitro inhibition of sPLA2-IIA-induces surfactant phospholipid hydrolysis correlates with the concentration of SP-A in surfactant. Intratracheal administration of sPLA2-IIA to mice causes hydrolysis of surfactant phosphatidylglycerol. Interestingly, such hydrolysis is significantly higher for SP-A gene-targeted mice, showing the in vivo inhibitory effect of SP-A on sPLA2-IIA activity. Administration of sPLA2-IIA also induces respiratory distress, which is more pronounced in SP-A gene-targeted mice than in wild-type mice. We conclude that SP-A inhibits sPLA2 activity, which may play a protective role by maintaining surfactant integrity during lung injury.
Cutting Edge: Invariant Vα14 NKT Cells Are Required for Allergen-Induced Airway Inflammation and Hyperreactivity in an Experimental Asthma Model
Authors: Lisbonne Mariette , Diem Séverine , de Castro Keller Alexandre , Lefort Jean , Araujo Luiza M. , Hachem Patricia , Fourneau Jean-Marie , Sidobre Stéphane , Kronenberg Mitchell , Taniguchi Masuru , Van Endert Peter , Dy Michel , Askenase Philip , Russo Momtchilo , Vargaftig B. Boris , Herbelin André , Leite-de-Moraes Maria C. 
Published: April 2014

AbstractAirway hyperreactivity (AHR), eosinophilic inflammation with a Th2-type cytokine profile, and specific Th2-mediated IgE production characterize allergic asthma. In this paper, we show that OVA-immunized Jα18−/− mice, which are exclusively deficient in the invariant Vα14+ (iVα14), CD1d-restricted NKT cells, exhibit impaired AHR and airway eosinophilia, decreased IL-4 and IL-5 production in bronchoalveolar lavage fluid, and reduced OVA-specific IgE compared with wild-type (WT) littermates. Adoptive transfer of WT iVα14 NKT cells fully reconstitutes the capacity of Jα18−/− mice to develop allergic asthma. Also, specific tetramer staining shows that OVA-immunized WT mice have activated (CD69+) iVα14 NKT cells. Importantly, anti-CD1d mAb treatment blocked the ability of iVα14 T cells to amplify eosinophil recruitment to airways, and both Th2 cytokine and IgE production following OVA challenge. In conclusion, these findings clearly demonstrate that iVα14 NKT cells are required to participate in allergen-induced Th2 airway inflammation through a CD1d-dependent mechanism.
Cutting Edge: The B Cell Chemokine CXC Chemokine Ligand 13/B Lymphocyte Chemoattractant Is Expressed in the High Endothelial Venules of Lymph Nodes and Peyer’s Patches and Affects B Cell Trafficking Across High Endothelial Venules
Authors: Ebisuno Yukihiko , Tanaka Toshiyuki , Kanemitsu Naotoshi , Kanda Hidenobu , Yamaguchi Kazuhito , Kaisho Tsuneyasu , Akira Shizuo , Miyasaka Masayuki 
Published: April 2014

Abstract
While CCR7 ligands direct T cell trafficking into lymph nodes (LNs) and Peyer’s patches (PPs), chemokines that regulate B cell trafficking across high endothelial venules (HEVs) remain to be fully elucidated. Here we report that CXC chemokine ligand (CXCL)13 (B lymphocyte chemoattractant) is detected immunohistologically in the majority of HEVs in LNs and PPs of nonimmunized mice. Systemically administered anti-CXCL13 Ab bound to the surface of ∼50% of HEVs in LNs and PPs, but not to other types of blood vessels, indicating that CXCL13 is expressed in the HEV lumen. In CXCL13-null mice, B cells rarely adhered to PP HEVs, whereas T cells did efficiently. Superfusion of CXCL13-null PPs with CXCL13 restored the luminal presentation of CXCL13 and also B cell arrest in PP HEVs at least partially. Collectively, these results indicate that CXCL13 expressed in the HEV lumen plays a crucial role in B cell trafficking into secondary lymphoid tissues such as PPs.
Cutting Edge: SR-PSOX/CXC Chemokine Ligand 16 Mediates Bacterial Phagocytosis by APCs Through its Chemokine Domain
Authors: Shimaoka Takeshi , Nakayama Takashi , Kume Noriaki , Takahashi Shu , Yamaguchi Junko , Minami Manabu , Hayashida Kazutaka , Kita Toru , Ohsumi Jun , Yoshie Osamu , Yonehara Shin 
Published: April 2014

AbstractSR-PSOX and CXC chemokine ligand (CXCL)16, which were originally identified as a scavenger receptor and a transmembrane-type chemokine, respectively, are indicated to be identical. In this study, we demonstrate that membrane-bound SR-PSOX/CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria. Importantly, our prepared anti-SR-PSOX mAb, which suppressed chemotactic activity of SR-PSOX, significantly inhibited bacterial phagocytosis by human APCs including dendritic cells. Various scavenger receptor ligands inhibited the bacterial phagocytosis of SR-PSOX. In addition, the recognition specificity for bacteria was determined by only the chemokine domain of SR-PSOX/CXCL16. Thus, SR-PSOX/CXCL16 may play an important role in facilitating uptake of various pathogens and chemotaxis of T and NKT cells by APCs through its chemokine domain.
Cutting Edge: Induced Indoleamine 2,3 Dioxygenase Expression in Dendritic Cell Subsets Suppresses T Cell Clonal Expansion
Authors: Mellor Andrew L. , Baban Babak , Chandler Phillip , Marshall Brendan , Jhaver Kanchan , Hansen Anna , Koni Pandelakis A. , Iwashima Makio , Munn David H. 
Published: April 2014

Abstract
In mice, immunoregulatory APCs express the dendritic cell (DC) marker CD11c, and one or more distinctive markers (CD8α, B220, DX5). In this study, we show that expression of the tryptophan-degrading enzyme indoleamine 2,3 dioxygenase (IDO) is selectively induced in specific splenic DC subsets when mice were exposed to the synthetic immunomodulatory reagent CTLA4-Ig. CTLA4-Ig did not induce IDO expression in macrophages or lymphoid cells. Induction of IDO completely blocked clonal expansion of T cells from TCR transgenic mice following adoptive transfer, whereas CTLA4-Ig treatment did not block T cell clonal expansion in IDO-deficient recipients. Thus, IDO expression is an inducible feature of specific subsets of DCs, and provides a potential mechanistic explanation for their T cell regulatory properties.
Germinal Centers Regulate Human Th2 Development
Authors: Johansson-Lindbom Bengt , Ingvarsson Sigurdur , Borrebaeck Carl A. K. 
Published: April 2014

Abstract
In the present study we demonstrate that all CD4+ T cells in human tonsil expressing the Th2-selective receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) also 1) express high levels of CXCR5, and 2) display a transitional CD45RA/RO phenotype and consistently do not produce significant amounts of cytokines when immediately analyzed ex vivo. Hence, they represent precursors of Th2 effector cells, a conclusion confirmed by their robust production of IL-4, IL-5, and IL-13, but not IFN-γ, after in vitro activation. CD4+ T cells, which express only intermediate levels of CXCR5, instead develop into IFN-γ-producing cells under identical culture conditions, thus establishing a correlation between relative levels of CXCR5 expression and the acquired cytokine profile. Because CXCR5 is critically involved in follicular localization, the results suggest that these CRTH2+ Th2 cells preferentially develop their cytokine-producing phenotype within germinal centers (GCs), whereas extrafollicular differentiation instead promotes Th1 development. In support for this proposal, we show that T cells with an intermediate expression of CXCR5 can be forced to also produce IL-4 and IL-13 if cultured with allogenic GC B cells. Finally, we demonstrate that the previously described CD57+ GC T cells also express high levels of CXCR5 but instead of comprising a Th2 precursor, they represent anergized T cells. Taken together, these data suggest that GCs and B cells regulate CD4+ T cell differentiation in a finely tuned fashion, either by promoting differentiation of Th2 cells, which apparently leave the lymphoid tissue before evolving a cytokine-producing phenotype, or by furnishing T cell unresponsiveness.
Lymphocyte Accumulation in the Spleen of Retinoic Acid Receptor-Related Orphan Receptor γ-Deficient Mice
Authors: Zhang Nu , Guo Jian , He You-Wen 
Published: April 2014

AbstractThe hormone nuclear receptor retinoic acid receptor-related orphan receptor γ (RORγ) plays important roles in thymocyte development and lymphoid organogenesis. RORγ and its thymus-specific isoform RORγt are expressed in the thymus, but not in the spleen and bone marrow (BM). However, RORγ−/− mice have 2- to 3-fold more splenocytes than wild-type controls due to an accumulation of conventional resting B lymphocytes. The increase in B lymphocytes in RORγ−/− mice is caused neither by abnormal B cell development in the BM nor by an obvious defect in the peripheral T cell compartment. Furthermore, analyses of BM chimeras using either RORγ−/− or recombinase-activating gene-2−/− mice as recipients and wild-type or RORγ−/− mice as donors, respectively, demonstrate that the splenic microenvironment of RORγ−/− mice is defective, since wild-type T and B lymphocytes accumulated in these chimeric mice. In addition, T lymphocyte homeostasis was altered due to a lowered thymic output in RORγ−/− mice. Collectively, these results suggest that RORγ regulates lymphocyte homeostasis at multiple levels.
Mechanisms of Ganglioside Inhibition of APC Function
Authors: Caldwell Sheila , Heitger Andreas , Shen Weiping , Liu Yihui , Taylor Barbara , Ladisch Stephan 
Published: April 2014

AbstractGangliosides shed by tumor cells exert potent inhibitory effects on cellular immune responses. Here we have studied ganglioside inhibition of APC function. When human monocytes were preincubated in 50 μM highly purified ganglioside GD1a, pulsed with tetanus toxoid (TT), and washed, the expected Ag-induced proliferative response of autologous normal T cells added to these monocytes was inhibited by 81%. Strikingly, there was also almost complete (92%) and selective inhibition of the up-regulation of the monocyte costimulatory molecule CD80, while I-CAM-1, LFA-3, HLA-DR, and CD86 expression were unaffected. Purified LPS-stimulated monocytes that had been preincubated in GD1a likewise showed inhibition of CD80 up-regulation (59%) as well as down-regulation of CD40 (54%) and impaired release of IL-12 and TNF-α (reduced by 59 and 51%). GD1a-preincubated human dendritic cells (DC) were also affected. They had reduced constitutive expression of CD40 (33%) and CD80 (61%), but not CD86, and marked inhibition of release of IL-6 (72%), IL-12 (70%), and TNF-α (46%). Even when pulsed with TT, these ganglioside-preincubated DC remained deficient in costimulatory molecule expression and cytokine secretion and were unable to induce a normal T cell proliferative response to TT. Finally, significant inhibition of nuclear localization of NF-κB proteins in activated DC suggests that disruption of NF-κB activation may be one mechanism contributing to ganglioside interference with APC expression of costimulatory molecules and cytokine secretion, which, in turn, may diminish antitumor immune responses.
Plasma Cell Survival Is Mediated by Synergistic Effects of Cytokines and Adhesion-Dependent Signals
Authors: Cassese Giuliana , Arce Sergio , Hauser Anja E. , Lehnert Katja , Moewes Beate , Mostarac Miro , Muehlinghaus Gwendolin , Szyska Martin , Radbruch Andreas , Manz Rudolf A. 
Published: April 2014

AbstractRecent results suggest that plasma cell longevity is not an intrinsic capacity, but depends on yet unknown factors produced in their environment. In this study, we show that the cytokines IL-5, IL-6, TNF-α, and stromal cell-derived factor-1α as well as signaling via CD44 support the survival of isolated bone marrow plasma cells. The cytokines IL-7 and stem cell factor, crucially important for early B cell development, do not mediate plasma cell survival, indicating that plasma cells and early B cells have different survival requirements. As shown in IL-6-deficient mice, IL-6 is required for a normal induction, but not for the maintenance of plasma cell responses in vivo, indicating that the effects of individual survival factors are redundant. Optimal survival of isolated plasma cells requires stimulation by a combination of factors acting synergistically. These results strongly support the concept that plasma cell survival depends on niches in which a combination of specific signals, including IL-5, IL-6, stromal cell-derived factor-1α, TNF-α, and ligands for CD44, provides an environment required to mediate plasma cell longevity.
Differential Localization and Function of ADP-Ribosylation Factor-6 in Anergic Human T Cells: A Potential Marker for Their Identification
Authors: Tzachanis Dimitrios , Appleman Leonard J. , van Puijenbroek Andre A. F. L. , Berezovskaya Alla , Nadler Lee M. , Boussiotis Vassiliki A. 
Published: April 2014

AbstractAnergy is a state of immunologic tolerance in which T cells are viable but incapable of responding to antigenic stimulation. Recent data indicate that anergic cells have a distinct gene expression program that determines their unique function. In this study we show that anergic human T cells selectively express the small GTPase ADP-ribosylation factor-6 (ARF6), which is involved in membrane traffic and regulation of the cortical actin cytoskeleton. ARF6 was expressed in the GTP-bound form that localizes at the plasma membrane, resulting in a distinct morphologic appearance of anergic cells. Forced expression of ARF6-GTP in Jurkat T cells prevented TCR-mediated reorganization of cortical actin, extracellular signal-regulated kinase1/2 activation, and IL-2 transcription. Forced expression of ARF6-GTP in primary human T cells inhibited extracellular signal-regulated kinase1/2 activation and proliferative responses. Importantly, T cells with the distribution pattern of ARF6-GTP were detected in peripheral blood, suggesting that anergic T cells may constitutively exist in vivo.
Functional Dissection of Lupus Susceptibility Loci on the New Zealand Black Mouse Chromosome 1: Evidence for Independent Genetic Loci Affecting T and B Cell Activation
Authors: Wither Joan E. , Lajoie Ginette , Heinrichs Svinda , Cai Yong-Chun , Chang Nan , Ciofani Amelia , Cheung Yui-Ho , MacLeod Ralph 
Published: April 2014

AbstractIn previous work, we demonstrated linkage between a broad region on New Zealand Black (NZB) chromosome 1 and increased costimulatory molecule expression on B cells and autoantibody production. In this study, we produced C57BL/6 congenic mice with homozygous NZB chromosome 1 intervals of differing lengths. We show that both B6.NZBc1(35–106) (numbers denote chromosomal interval length) and B6.NZBc1(85–106) mice produce IgG anti-nuclear autoantibodies, but B6.NZBc1(35–106) mice develop significantly higher titers of autoantibodies and more severe renal disease than B6.NZBc1(85–106) mice. Cellular analysis of B6.NZBc1(85–106) mice revealed splenomegaly and increased numbers of memory T cells. In addition to these features, B6.NZBc1(35–106) mice had altered B and T cell activation with increased expression of CD69, and for B cells, costimulatory molecules and MHC. Introduction of an anti-hen egg white lysozyme Ig transgene, as a representative nonself-reactive Ig receptor, onto the B6.NZBc1(35–106) background corrected the B cell activation phenotype and led to dramatic normalization of splenomegaly and T cell activation, but had little impact on the increased proportion of memory T cells. These findings indicate that there are multiple lupus susceptibility genes on NZB chromosome 1, and that although B cell defects play an important role in lupus pathogenesis in these mice, they act in concert with T cell activation defects.
Selective Inhibition of T Cell Activation Via CD147 Through Novel Modulation of Lipid Rafts
Authors: Staffler Günther , Szekeres Andreas , Schütz Gerhard J. , Säemann Marcus D. , Prager Elisabeth , Zeyda Maximilian , Drbal Karel , Zlabinger Gerhard J. , Stulnig Thomas M. , Stockinger Hannes 
Published: April 2014

AbstractThe plasma membrane is compartmentalized into microdomains and the association/dissociation of receptors and signaling molecules with/from these membrane domains is a major principle for regulation of signal transduction. By following the reorganization of microdomains on living cells and performing biochemical studies, we show that Ab targeting of the T cell activation-associated Ag CD147 prevents TCR stimulation-dependent reorganization and clustering of microdomains. Triggering CD147 induces a displacement of the GPI-anchored coreceptors CD48 and CD59 from microdomains in human T lymphocytes. This perturbation of microdomains is accompanied by a selective inhibition of TCR-mediated T cell proliferation. The CD147-inhibited cells secret normal levels of IL-2 but acquire reduced amounts of the IL-2 receptor α-chain CD25. These results indicate that negative regulating signals can modulate microdomains and suggest a general mechanism for inhibition of receptor signaling.
Blastocyst MHC, a Putative Murine Homologue of HLA-G, Protects TAP-Deficient Tumor Cells from Natural Killer Cell-Mediated Rejection In Vivo
Authors: Tajima Atsushi , Tanaka Toshitaka , Ebata Tomohiko , Takeda Kazuyoshi , Kawasaki Akemi , Kelly Janice M. , Darcy Phillip K. , Vance Russell E. , Raulet David H. , Kinoshita Katsuyuki , Okumura Ko , Smyth Mark J. , Yagita Hideo 
Published: April 2014

AbstractBlastocyst MHC is a recently identified mouse MHC class Ib gene, which is selectively expressed in blastocyst and placenta, and may be the mouse homolog of HLA-G gene the products of which have been implicated in protection of fetal trophoblasts from maternal NK cells and evasion of some tumor cells from NK cell attack. In this study, we identified two blastocyst MHC gene transcripts encoding a full-length α-chain (bc1) and an alternatively spliced form lacking the α2 domain (bc2), which may be homologous to HLA-G1 and HLA-G2, respectively. Both placenta and a teratocarcinoma cell line predominantly expressed the bc2 transcript. When these cDNAs were expressed in TAP-deficient RMA-S or TAP-sufficient RMA cells, only bc1 protein was expressed on the surface of RMA cells, but both bc1 and bc2 proteins were retained in the cytoplasm of RMA-S cells. Significantly, the RMA-S cells expressing either bc1 or bc2 were protected from lysis by NK cells in vitro. This protection was at least partly mediated by up-regulation of Qa-1b expression on the surface of RMA-S cells, which engaged the CD94/NKG2A inhibitory receptor on NK cells. More importantly, the bc1- or bc2-expressing RMA-S cells were significantly protected from NK cell-mediated rejection in vivo. These results suggested a role for blastocyst MHC in protecting TAP-deficient trophoblasts and tumor cells from NK cell attack in vivo.
CCR3 Expression Induced by IL-2 and IL-4 Functioning as a Death Receptor for B Cells
Authors: Jinquan Tan , Jacobi Henrik H. , Jing Chen , Millner Anders , Sten Eva , Hviid Lars , Anting Liu , Ryder Lars P. , Glue Christian , Skov Per S. , Jarman Elizabeth , Lamberth Kasper , Malling Hans-Jørgen , Poulsen Lars K. 
Published: April 2014

AbstractWe report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (∼98% CCR3+). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19+ (∼40% apoptotic cells) B cell cultures as well as B cell lines, but has no effect on chemotaxis or cell adhesion. Freshly isolated B cells express low levels of CD95 and CD95 ligand (CD95L) (19 and 21%, respectively). Expression is up-regulated on culture in the presence of a combination of IL-2, IL-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant death signaling pathways, which include an increase in levels of Bcl-2 expression, its functional activity, and the release of cytochrome c from the mitochondria into the cytosol. These events initiate a cascade of enzymatic processes of the caspase family, culminating in programmed cell death. Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests a therapeutic modality in the treatment of B cell lymphoma.
Synoviocyte-Mediated Expansion of Inflammatory T Cells in Rheumatoid Synovitis Is Dependent on CD47-Thrombospondin 1 Interaction
Authors: Vallejo Abbe N. , Yang Hongyu , Klimiuk Piotr A. , Weyand Cornelia M. , Goronzy Jörg J. 
Published: April 2014

AbstractFibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis elicit spontaneous proliferation of autologous T cells in an HLA-DR and CD47 costimulation-dependent manner. T cell costimulation through CD47 is attributed to specific interaction with thrombospondin-1 (TSP1), a CD47 ligand displayed on FLS. CD47 binding by FLS has broad biological impact that includes adhesion and the triggering of specific costimulatory signals. TSP1+ FLS are highly adhesive to T cells and support their aggregation and growth in situ. Long-term cultures of T cells and FLS form heterotypic foci that are amenable to propagation without exogenous growth factors. T cell adhesion and aggregate formation on TSP1+ FLS substrates are inhibited by CD47-binding peptides. In contrast, FLS from arthroscopy controls lack adhesive or T cell growth-promoting activities. CD47 stimulation transduces a costimulatory signal different from that of CD28, producing a gene expression profile that included induction of ferritin L chain, a component of the inflammatory response. Ferritin L chain augments CD3-induced proliferation of T cells. Collectively, these results demonstrate the active role of FLS in the recruitment, activation, and expansion of T cells in a CD47-dependent manner. Because TSP1 is abundantly expressed in the rheumatoid synovium, CD47-TSP1 interaction is proposed to be a key component of an FLS/T cell regulatory circuit that perpetuates the inflammatory process in the rheumatoid joint.