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European Journal of Immunology

Mikiko Tohyama, Yuji Shirakata, Yasushi Hanakawa, Xiuju Dai, Ken Shiraishi, Masamoto Murakami, Saori Miyawaki, Hideki Mori, Ryo Utsunomiya, Kana Masuda, Koji Hashimoto, Koji Sayama
IL-22 induces STAT3 phosphorylation and mediates psoriasis-related gene expression. However, the signaling mechanism leading from pSTAT3 to the expression of these genes remains unclear. We focused on Bcl-3, which is induced by STAT3 activation and mediates gene expression. In cultured human epidermal keratinocytes, IL-22 increased Bcl-3, which was translocated to the nucleus with p50 via STAT3 activation. The increases in CXCL8, S100As and human β-defensin 2 mRNA expression caused by IL-22 were abolished by siRNA against Bcl-3...
September 12, 2017: European Journal of Immunology
Alessandro Nasti, Yoshio Sakai, Akihiro Seki, Geraldine Belen Buffa, Takuya Komura, Hatsune Mochida, Masatoshi Yamato, Keiko Yoshida, Tuyen T B Ho, Masayuki Takamura, Soichiro Usui, Takashi Wada, Masao Honda, Shuichi Kaneko
Stromal cells in adipose tissue are useful for repair/regenerative therapy as they harbor a substantial number of mesenchymal stem cells; therefore, freshly isolated autologous uncultured adipose tissue-derived stromal cells (u-ADSCs) are useful for regenerative therapy, and obviate the need for mesenchymal stem cells. We evaluated the therapeutic effect of murine u-ADSCs and sorted subsets of u-ADSCs in a concanavalin A (ConA)-induced murine model of hepatitis, as well as their characteristics. We found that 10% to 20% of u-ADSCs expressed the CD45 leukocyte-related antigen...
September 11, 2017: European Journal of Immunology
Aude Aubatin, Nouhoum Sako, Xavier Decrouy, Emmanuel Donnadieu, Valérie Molinier-Frenkel, Flavia Castellano
Amino-acid catabolizing enzymes produced by mononuclear phagocytes play a central role in regulating the immune response. The mammalian phenylalanine-catabolizing enzyme IL4-induced gene 1 (IL4I1) inhibits effector T lymphocyte proliferation and facilitates regulatory T-cell development. IL4I1 expression by macrophages of various human tumors may affect patient prognosis as it facilitates tumor escape from the T-cell response in murine models. Its enzymatic activity appears to participate in its effects, but some actions of IL4I1 remain unclear...
September 10, 2017: European Journal of Immunology
Michael Friedrich, Katharina Pracht, Mir-Farzin Mashreghi, Hans-Martin Jäck, Andreas Radbruch, Barbara Seliger
MicroRNAs (miRNAs) are endogenously encoded ∼22 nt small non-coding RNAs. They function as key players of many cellular processes by base pairing with target mRNAs and thereby impairing gene expression at the post-transcriptional level. Recent findings demonstrate a critical role of many miRNAs in immune cell differentiation and immune responses, which is also associated with the development and progression of many tumor and non-tumor diseases. Here we review the multifaceted miRNA-148/-152 family members consisting of miR-148a, miR-148b and miR-152...
September 7, 2017: European Journal of Immunology
Jakob Zimmermann, Pawel Durek, Anja A Kühl, Florian Schattenberg, Patrick Maschmeyer, Francesco Siracusa, Katrin Lehmann, Kerstin Westendorf, Melanie Weber, René Riedel, Susann Müller, Andreas Radbruch, Hyun-Dong Chang
Conflicting evidence has been provided as to whether induction of intestinal inflammation by adoptive transfer of naïve T cells into Rag(-/-) mice requires expression of the transcription factor T-bet by the T cells. Here, we formally show that the intestinal microbiota composition of the Rag(-/-) recipient determines whether or not T-bet-deficient Th cells can induce colitis and we have resolved the differences of the two microbiomes, permissive or non-permissive to T-bet-independent colitis. Our data highlight the dominance of the microbiota over particular T cell differentiation programs in the pathogenesis of chronic intestinal inflammation...
September 6, 2017: European Journal of Immunology
Akihiro Yoshikawa, Kevin Bi, Derin B Keskin, Guanglang Zhang, Bruce Reinhold, Ellis L Reinherz
To investigate the role of TCR-pMHC interaction in regulating lung CD8 tissue-resident T cell (TR ) differentiation, polyclonal responses were compared against NP366-374 /D(b) and PA224-233 /D(b) , two immunodominant epitopes that arise during influenza A infection in mice. Memory niches distinct from iBALTs develop within the lamina propria, supporting CD103+ and CD103- CD8 TR generation and intraepithelial translocation. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) identify dominant TCR, adherence junction, RIG-I-like and NOD-like pattern recognition receptor as well as TGFβ signaling pathways and memory signatures among PA224-233 /D(b) T cells consistent with T resident memory (TRM ) status...
September 5, 2017: European Journal of Immunology
Irina Gurevich, Tali Feferman, Idan Milo, Orna Tal, Ofra Golani, Ingo Drexler, Guy Shakhar
Antigen (Ag)-specific activation of naïve T cells by migrating dendritic cells (DCs) is a highly efficient process, although the chances for their co-localization in lymph nodes (LNs) appear low. Ag presentation may be delegated from Ag-donor DCs to the abundant resident DCs, but the routes of Ag transfer and how it facilitates T-cell activation remain unclear. We visualized CD8(+) T cell-DC interactions to study the sites, routes and cells mediating Ag transfer in mice. In vitro, Ag transfer from isolated ovalbumin (OVA)(+) bone marrow (BM)-DCs triggered widespread arrest, Ca(2+) flux and CD69 upregulation in OT-I T cells contacting recipient DCs...
September 5, 2017: European Journal of Immunology
Dylan Sheerin, Peter Jm Openshaw, Andrew J Pollard
Vaccination is a principal and highly cost-effective means of controlling infectious diseases, providing direct protection against pathogens by conferring long-lasting immunological memory and inducing population-level herd immunity. Despite rapid ongoing progress in vaccinology, there remain many obstacles to the development and deployment of novel or improved vaccines; these include the underlying science of how to induce and sustain appropriate protective immune responses as well as bureaucratic, logistic and socio-political hurdles...
September 1, 2017: European Journal of Immunology
Verena Schmitt, Madelaine Hahn, Verena Kästele, Olga Wagner, Maximilian Wiendl, Anja Derer, Adriano Taddeo, Stefanie Hahne, Andreas Radbruch, Hans-Martin Jäck, Wolfgang Schuh, Dirk Mielenz, Steffen Gay, Georg Schett, Axel J Hueber, Silke Frey
The IL-1 family member IL-36α has proinflammatory and pathogenic properties in psoriasis. IL-36α binds to the IL-36 receptor leading to nuclear factor kappa B/mitogen activated protein kinase mediated cytokine release. The IL-36R antagonist prevents recruitment of IL-1 receptor accessory protein and therefore IL-36-dependent cell activation. In inflamed human tissue, we previously could show that resident B cells and plasma cells (PC) express IL-36α. Further, fibroblast-like synoviocytes (FLS) produced proinflammatory cytokines upon IL-36α-stimulation...
August 31, 2017: European Journal of Immunology
Sarah Fleischer, Stefanie Ries, Ping Shen, Alix Lheritier, Frédéric Cazals, Gerd R Burmester, Thomas Dörner, Simon Fillatreau
Rheumatoid arthritis (RA) is associated with abnormal B cell functions implicating antibody-dependent and -independent mechanisms. B cells have emerged as important cytokine-producing cells, and cytokines are well-known drivers of RA pathogenesis. To identify novel cytokine-mediated B cell functions in RA, we comprehensively analysed the capacity of B cells from RA patients with an inadequate response to disease modifying anti-rheumatic drugs to produce cytokines in comparison with healthy donors (HD). RA B cells displayed a constitutively higher production of the pathogenic factors interleukin (IL)-8 and Gro-α, while their production of several cytokines upon activation via the B cell receptor for antigen (BCR) was broadly suppressed, including a loss of the expression of the protective factor TRAIL, compared to HD B cells...
August 29, 2017: European Journal of Immunology
Maike Becker, Megan K Levings, Carolin Daniel
Obesity and type-2 diabetes (T2D) are associated with metabolic defects and inflammatory processes in fat depots. FoxP3(+) regulatory T cells (Tregs) control immune tolerance, and have an important role in controlling tissue-specific inflammation. In this mini-review we will discuss current insights into how cross-talk between T cells and adipose tissue shapes the inflammatory environment in obesity-associated metabolic diseases, focusing on the role of CD4(+) T cells and Tregs. We will also highlight potential opportunities for how the immunoregulatory properties of Tregs could be harnessed to control inflammation in obesity and T2D and emphasize the critical need for more research on humans to establish mechanisms that are conserved in both mice and humans...
August 28, 2017: European Journal of Immunology
Scott N Mueller
Dendritic cells (DC) are specialized in the processing and presentation of antigen for the activation of lymphocytes. Multiple subsets of DCs exist with distinct functions and roles in the initiation of immune responses. DCs found within tissues acquire antigens or become infected by pathogens and migrate to local draining lymph nodes (LN) where they can directly stimulate T cells. These migratory DCs can also transfer antigens to LN-resident DCs and may indirectly enhance T cell priming. In this issue of the European Journal of Immunology, Gurevich et al...
August 28, 2017: European Journal of Immunology
David Schub, Mathias Fousse, Klaus Faßbender, Barbara C Gärtner, Urban Sester, Martina Sester, Tina Schmidt
BACKGROUND: VZV-reactivation may lead to symptomatic central nervous system (CNS) diseases, but identification of VZV as causative pathogen of CNS-diseases is challenging. This study was performed to characterize VZV-specific T-cells from cerebrospinal fluid (CSF) and blood of patients with active CNS-disease and to determine whether this may improve differential diagnosis. METHODS: 27 patients with pleocytosis in the CSF were recruited and classified into three groups (10 VZV-related, 10 non-VZV-related, 7 unclear)...
August 28, 2017: European Journal of Immunology
Line Victoria Moen, Zeynep Sener, Roman Volchenkov, Anja Camilla Svarstad, Aud Marit Eriksen, Halvor L Holen, Bjørn S Skålhegg
Protein kinase A (PKA) is a holoenzyme composed of a regulatory subunit dimer and two catalytic subunits and regulates numerous cellular functions including immune cell activity. There are two major catalytic subunit genes, PRKACA and PRKACB encoding the catalytic subunits Cα and Cβ. The PRKACB gene encodes several splice variants including Cβ2, which is enriched in T-, B- and natural killer cells. Cβ2 is significantly larger (46 kDa) than any other C splice variant. In this study we characterized mice ablated for the Cβ2 protein demonstrating a significantly reduced cAMP-induced catalytic activity of PKA in the spleenocytes, lymphocytes and thymocytes...
August 24, 2017: European Journal of Immunology
Allison K Ehrlich, Jamie M Pennington, Susan Tilton, Xisheng Wang, Nikki B Marshall, Diana Rohlman, Castle Funatake, Sumit Punj, Edmond O'Donnell, Zhen Yu, Siva K Kolluri, Nancy I Kerkvliet
Activation of the aryl hydrocarbon receptor (AhR) by immunosuppressive ligands promotes the development of regulatory T (Treg) cells. Although AhR-induced Foxp3(+) Treg cells have been well studied, much less is known about the development and fate of AhR-induced Type 1 Treg (AhR-Tr1) cells. In the current study, we identified the unique transcriptional and functional changes in murine CD4(+) T cells that accompany the differentiation of AhR-Tr1 cells during the CD4(+) T-cell-dependent phase of an allospecific cytotoxic T lymphocyte (allo-CTL) response...
August 23, 2017: European Journal of Immunology
Julius C Fischer, Vera Otten, Katja Steiger, Martina Schmickl, Julia Slotta-Huspenina, Rudi Beyaert, Geert van Loo, Christian Peschel, Hendrik Poeck, Tobias Haas, Silvia Spoerl
The NF-κB regulator A20 limits inflammation by providing negative feedback in myeloid cells and B cells. Functional lack of A20 has been linked to several inflammatory and autoimmune diseases. To define how A20 affects the functionality of T effector cells in a highly inflammatory environment, we performed conventional allogeneic hematopoietic stem cell transplantation (allo-HSCT) with A20-deficient CD4(+) and CD8(+) donor T cells in mice. Severity and mortality of graft-versus-host disease (GVHD) after allo-HSCT was drastically reduced in recipients transplanted with conventional doses of A20-deficient T cells...
August 22, 2017: European Journal of Immunology
Jo-Anne Chan, Danielle I Stanisic, Michael F Duffy, Leanne J Robinson, Enmoore Lin, James W Kazura, Christopher L King, Peter M Siba, Freya Ji Fowkes, Ivo Mueller, James G Beeson
Acquired antibodies play an important role in immunity to P. falciparum malaria and are typically directed towards surface antigens expressed by merozoites and infected erythrocytes (IEs). The importance of specific IE surface antigens as immune targets remains unclear. We evaluated antibodies and protective associations in two cohorts of children in Papua New Guinea. We used genetically-modified P. falciparum to evaluate the importance of PfEMP1 and a P. falciparum isolate with a virulent phenotype. Our findings suggested that PfEMP1 was the dominant target of antibodies to the IE surface, including functional antibodies that promoted opsonic phagocytosis by monocytes...
August 20, 2017: European Journal of Immunology
Maria Pasztoi, Joern Pezoldt, Michael Beckstette, Christoph Lipps, Dagmar Wirth, Manfred Rohde, Krisztina Paloczi, Edit Iren Buzas, Jochen Huehn
Intestinal regulatory T cells (Tregs) are fundamental in peripheral tolerance towards commensals and food-borne antigens. Accordingly, gut-draining mesenteric lymph nodes (mLNs) represent a site of efficient peripheral de novo Treg induction when compared to skin-draining peripheral LNs (pLNs), and we had recently shown that LN stromal cells substantially contribute to this process. Here, we aimed to unravel the underlying molecular mechanisms and generated immortalized fibroblastic reticular cell lines (iFRCs) from mLNs and pLNs, allowing unlimited investigation of this rare stromal cell subset...
August 18, 2017: European Journal of Immunology
Marco van Ham, René Teich, Lars Philipsen, Jana Niemz, Nicole Amsberg, Josef Wissing, Manfred Nimtz, Lothar Gröbe, Stefanie Kliche, Nadine Thiel, Frank Klawonn, Mario Hubo, Helmut Jonuleit, Peter Reichardt, Andreas J Müller, Jochen Huehn, Lothar Jänsch
Regulatory T (Treg) cells require T-cell receptor (TCR) signalling to exert their immunosuppressive activity, but the precise organization of the TCR signalling network compared to conventional T (Tconv) cells remains elusive. By using accurate mass spectrometry and multi-epitope ligand cartography (MELC) we characterized TCR signalling and recruitment of TCR signalling components to the immunological synapse (IS) in Treg cells and Tconv cells. With the exception of Themis which we detected in lower amounts in Treg cells, other major TCR signalling components were found equally abundant, however, their phosphorylation-status notably discriminates Treg cells from Tconv cells...
August 17, 2017: European Journal of Immunology
Fabian Mohr, Julius Clemens Fischer, Marc Nikolaus, Christian Stemberger, Stefan Dreher, Admar Verschoor, Tobias Haas, Hendrik Poeck, Dirk H Busch
The transfer of regulatory T cells, either freshly isolated, or modified, represents a promising therapeutic approach to dampen misdirected immune responses, like autoimmune diseases, chronic inflammatory syndromes and graft versus host disease. Clinical isolation of highly pure regulatory T cell (Treg) populations is still challenging and labeling reagents can influence their viability and functionality, potentially altering the potency of isolated Treg cell products. Here we show that reversible Fab multimer-based Treg purification can prevent conventional antibody label-induced interferences in vitro and in vivo...
August 17, 2017: European Journal of Immunology
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