TlR expression profile of human gingival margin-derived stem progenitor cells

Background: Gingival margin-derived stem/progenitor cells (G-MSCs) show remarkable periodontal regenerative potential in vivo. During regeneration, G-MSCs may interact with their inflammatory environment via toll-likereceptors (TLRs). The present study aimed to depict the G-MSCs TLRs expression profile. Material and Methods: Cells were isolated from free gingival margins, STRO-1-immunomagnetically sorted and seeded to obtain single colony forming units (CFUs). G-MSCs were characterized for CD14, CD34, CD45, CD73, CD90, CD105, CD146 and STRO-1 expression, and for multilineage differentiation potential. Following G-MSCs’ incubation in basic or inflammatory medium (IL-1β, IFN-γ, IFN-α, TNF-α) a TLR expression profile was generated. Results: G-MSCs showed all stem/progenitor cells’ characteristics. In basic medium G-MSCs expressed TLRs 1, 2, 3, 4, 5, 6, 7, and 10. The inflammatory medium significantly up-regulated TLRs 1, 2, 4, 5, 7 and 10 and diminished TLR 6 (p≤0.05, Wilcoxon-Signed-Ranks-Test). Conclusions: The current study describes for the first time the distinctive TLRs expression profile of G-MSCs under uninflamed and inflamed conditions

Time-resolved in situ studies on the formation mechanism of iron oxide nanoparticles using combined fast-XANES and SAXS

The reaction of iron chlorides with an alkaline reagent is one of the most prominent methods for the synthesis of iron oxide nanoparticles. We studied the particle formation mechanism using triethanolamine as reactant and stabilizing agent. In situ fast-X-ray absorption near edge spectroscopy and small-angle X-ray scattering provide information on the oxidation state and the structural information at the same time. In situ data were complemented by ex situ transmission electron microscopy, wide-angle X-ray scattering and Raman analysis of the formed nanoparticles. The formation of maghemite nanoparticles (gamma-Fe2O3) from ferric and ferrous chloride was investigated. Prior to the formation of these nanoparticles, the formation and conversion of intermediate phases (akaganeite, iron(II, III) hydroxides) was observed which undergoes a morphological and structural collapse. The thus formed small magnetite nanoparticles (Fe3O4) grow further and convert to maghemite with increasing reaction time

Gamma Delta T Cells (γδ T Cells) in Health and Disease: In Memory of Professor Wendy Havran

Gamma delta (γδ) T cells are a small subset of CD3-positive T cells in the peripheral blood but occur at increased frequency in mucosal tissues [...]

Human γδ T lymphocytes for immunotherapeutic strategies against cancer

γδ T lymphocytes are a numerically small subset of T cells with potent cytotoxic activity against a variety of tumor cells. Human γδ T cells expressing the Vγ9Vδ2 T cell antigen receptor recognize endogenous pyrophosphate molecules that are overproduced in transformed cells. Moreover, the intracellular accumulation of such pyrophosphates is strongly enhanced by aminobisphosphonates used in the treatment of osteoporosis and bone metastasis in certain cancer patients. A new concept of cancer immunotherapy is based on the endogenous activation of γδ T cells with aminobisphosphonates plus low-dose interleukin-2

Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell-based therapeutic approaches

Glioblastoma, formerly known as glioblastoma multiforme (GBM), is the most frequent and most aggressive brain tumour in adults. The brain is an immunopriviledged organ, and the blood-brain barrier shields the brain from immune surveillance. In this review, we discuss the composition of the immunosuppressive tumour micromilieu and potential immune escape mechanisms in GBM. In this respect, we focus on the role of the NKG2D receptor/ligand system. NKG2D ligands are frequently expressed on GBM tumour cells and can activate NKG2D-expressing killer cells including NK cells and γδ T cells. Soluble NKG2D ligands, however, contribute to tumour escape from immunological attack. We also discuss the current immunotherapeutic strategies to improve the survival of GBM patients. Such approaches include the modulation of the NKG2D receptor/ligand system, the application of checkpoint inhibitors, the adoptive transfer of ex vivo expanded and/or modified immune cells or the application of antibodies and antibody constructs to target cytotoxic effector cells in vivo. In view of the multitude of pursued strategies, there is hope for improved overall survival of GBM patients in the future

Editorial: "Recent Advances in Gamma/Delta T Cell Biology: New Ligands, New Functions, and New Translational Perspectives"

Since their discovery in the mid-1980s, interest in the immunological significance of γδ T cells has been subject to oscillations. The initial excitement over the unexpected discovery of a second T cell receptor (TCR) was followed by years of uncertainty as to the biological importance of these ambivalent T cells. Major breakthroughs led to the identification of specific and unique antigens for the γδ TCR and accumulating evidence now shows that γδ T cells play a major role in local immunosurveillance, thereby controlling tumorigenesis. Since 2004, biannual international γδ T cell conferences are held to bring together experts in basic and clinical γδ T cell research. To make accessible and synthesize the body of knowledge that has been put together, to date, we have organized a “Research Topic” on γδ T cells consisting of a collection of original articles and focused reviews written by leading experts in the field. The idea of this Research Focus was to present the current status and “hot topics” as well as clinical perspectives on γδ T cell research

Vitamin C and Vitamin D-friends or foes in modulating γδ T-cell differentiation?

The differentiation and functional plasticity of T cells are transcriptionally and epigenetically regulated by signals imposed by the local cytokine milieu and a variety of additional factors, including vitamins. Vitamin C has pleiotropic functions in the immune system. It exerts antioxidant activity, can directly kill selected tumor targets, promotes early T-cell differentiation, and enhances Th1 cytokine production in mature T cells

Die Nationalparkregion als Kulisse für Regionalentwicklung - das Beispiel Nationalpark Hunsrück-Hochwald

Der im Jahr 2015 in Rheinland-Pfalz und dem Saarland eröffnete Nationalpark Hunsrück-Hochwald begeht in mehrfacher Hinsicht neue Wege: Die Ausweisung erfolgte im Zuge eines intensiven Bürgerbeteiligungsprozesses, der bis in die heutigen Steuerungsgremien hineinwirkt, und ist mit dem Ziel verbunden, in der gesetzlich verankerten Nationalparkregion einen weitreichenden Regionalentwicklungsprozess zu initiieren. Der kommunale Wille, ein Regionalmanagement für die Nationalparkregion einzurichten, verlangt nach der Analyse der vorhandenen Akteursstrukturen und ihrer Voraussetzung für eine kooperative Regionalentwicklung. Es stellt sich die Frage, welche Akteurskonstellation für das Regionalmanagement geeignet ist und wie es seiner koordinierenden Rolle vor dem Hintergrund der vorhandenen Kooperationsstrukturen sowie der Besonderheit als Nationalparkregion gerecht werden kann - Aspekte, die dieser Beitrag aufgreift.The national park Hunsrück-Hochwald was opened in 2015 in Rheinland-Pfalz and Saarland and breaks new ground in many respects. The designation of the park involved an intensive public participation process that continues to influence the management bodies of today. This is connected to the aim of initiating a far-reaching process of regional development in the legally designated national park region. To meet the local desire to establish regional management for the national park region it is necessary to undertake an analysis of existing structures of actors and related conditions for cooperative regional development. Consideration is given to which actor constellation is appropriate for regional management, how regional management can fulfil a coordinating role against the background of existing structures of cooperation, and how management can be made appropriate to the special character of the national park region

Tumor-Infiltrating γδ T Cells Suppress T and Dendritic Cell Function via Mechanisms Controlled by a Unique Toll-like Receptor Signaling Pathway

Summaryγδ T cells are important contributors to innate immunity against cancer, but their regulatory role in controlling immune responses remains largely unknown. Here we report that a dominant γδ1 T cell population among lymphocytes infiltrating breast tumors possessed a potent ability to suppress naive and effector T cell responses and to block the maturation and function of dendritic cells. Adoptive cotransfer experiments demonstrated their in vivo suppressive activity. However, their immunosuppressive activity could be reversed by human Toll-like receptor (TLR) 8 ligands both in vitro and in vivo. siRNA-mediated knockdown experiments revealed that MyD88, TRAF6, IKKα IKKβ, and p38α molecules in γδ1 cells were required for these cells to respond to TLR8 ligands, whereas TAK1, JNK, and ERK molecules did not appear to be involved in functional regulation. These results provide new insights into the regulatory mechanisms of tumor-specific γδ T cells and identify a unique TLR8 signaling pathway linking to their functional regulation

Quantification of Malalignment and Corrective Osteotomies in Patients With Malunion After Elastic Stable Intramedullary Nailing of Pediatric Forearm Fractures

PURPOSE: This study looked at postoperative malunion with restricted function after elastic stable intramedullary nailing (ESIN) in pediatric patients in their childhood or adolescence. The primary objective was to compare the magnitude of the osseous malposition to the healthy opposite side. Second, these individuals were treated with patient-specific surgical instrumentation, and functional outcomes were documented. METHODS: Patients under the age of 18 at the time of a corrective osteotomy due to a forearm malunion after initial ESIN treatment were included in this study. The healthy contralateral side was used as a reference for preoperative analysis and planning of the osteotomy. Osteotomies were performed using patient-specific guides and the direction and extent of the malunion were compared to the change in range of motion (ROM) after the operation. RESULTS: Fifteen patients met the inclusion criteria at three years after initial ESIN placement, with the most pronounced malposition in the rotational axis. The postoperative function significantly improved by 12° (pre-op: 60° ± 17; post-op: 72° ± 10) of pronation and 33° (pre-op: 43° ± 26; post-op: 76° ± 13) of supination. There was no correlation between the amount and direction of malformation and the change in ROM. CONCLUSIONS: The most noticeable malunion after forearm fractures treated with the ESIN technique is in the rotational direction. Patient-specific corrective osteotomy of pediatric forearm malunion following forearm fracture fixation with ESIN achieves significant improvement in forearm range of motion. CLINICAL RELEVANCE: The findings are clinically relevant since forearm fractures are the most common pediatric fracture, affecting a large number of patients who can benefit from the findings of this study. It has the potential to raise awareness of the significance of the accurate rotational component of intraoperative bone alignment in the ESIN procedure