Group 3 innate lymphoid cells: regulating host-commensal bacteria interactions in inflammation and cancer.

Abstract A delicate balance exists between the mammalian immune system and normally beneficial commensal bacteria that colonize the gastrointestinal tract, which is necessary to maintain tissue homeostasis. Dysregulation of these interactions between the host and commensal bacteria is causally associated with chronic inflammation and the development of cancer. In contrast, recent reports have highlighted that commensal bacteria also play an essential role in promoting anti-tumor immune responses in several contexts, highlighting a paradox whereby interactions between the host and commensal bacteria can influence both pro- and anti-tumor immunity. Given the critical roles for group 3 innate lymphoid cells (ILC3s) in regulating inflammation, tissue repair and host–microbe interactions in the intestine, here we discuss new evidence that ILC3s may profoundly influence the development, progression and control of tumors. In this review, we provide an overview of recent advances in understanding the impact of commensal bacteria on tumorigenesis, discuss recent findings identifying ILC3s as critical regulators of host–microbe interactions and highlight the emerging role of this immune cell population in cancer and their potential implication as a therapeutic target.</jats:p

SmartTokens: Embedding Motion and Grip Sensing in Small Tangible Objects

International audienceSmartTokens are small-sized tangible tokens that can sense multiple types of motion, multiple types of touch/grip, and send input events wirelessly as state-machine transitions. By providing an open platform for embedding basic sensing capabilities within small form-factors, SmartTokens extend the design space of tangible user interfaces. We describe the de- sign and implementation of SmartTokens and illustrate how they can be used in practice by introducing a novel TUI design for event notification and personal task management

A Better Grasp on Pictures Under Glass: Comparing Touch and Tangible Object Manipulation using Physical Proxies

International audienceWe introduce a novel method based on physical proxies for investigating fundamental differences between touch and tangible interfaces. This method uses physical chips to emulate the flat, non-graspable objects that make up touch interfaces , in a way that supports direct comparison with tangible interfaces. We ran an experiment to test the effect of object thickness on participants' behavior, performance and subjective experience in spatial rearrangement tasks. We found that for the tasks tested, thick objects are faster but less accurate to operate, and that their graspability is only used occasionally. We also found that coarse manipulation of multiple thin objects is error-prone, an issue that only thick objects may allow to alleviate

Cellulose conversion to glycols over DUT-8(Ni) derived nickel-tungsten/carbons: selectivity tuning.

International audienceThere have been various studies on the transformation of cellulose to low carbon polyols (C2,3), ethylene glycol (EG), propylene glycol (PG) and glycerol (Gly), which are prevailing intermediates in the manufacture of plastics, pharmaceuticals, food additives, and cosmetics, etc. Cellulose conversion to diols mainly involves 3 types of reactions: cellulose hydrolysis, retro-aldol condensation, and hydrogenation. For the formation of 1,2-PG, the sugar isomerization reaction is also involved. Using activated carbon-supported tungsten carbide (W2C/AC) catalysts, Zhang et al. obtained an EG yield of 76 % starting from cellulose [1]. Besides being a cheap non-noble metal-derived phase, a noteworthy advantage of tungsten carbide over other tungsten species (oxides and metal) is the preferential formation of EG among other polyols due to its Pt-like catalytic behavior. Yang et al. prepared Ni-W/C nanofiber catalysts, in situ fabricated through the pyrolysis of Ni, W-containing metal-organic framework fibers. A large productivity varying from 15.3 to 70.8 molEG.h-1.gW-1 was reported, which is two orders of magnitude higher than previously reported Ni-W-based catalysts [2]. Interestingly Sun et al. [3] showed the impact of the Sn phase and valence on the catalytic properties of bimetallic systems supported on activated carbon. When powder of metallic Sn was used with Ni/AC, a Ni-Sn alloy formed which promoted retro-aldol cleavage and hydrogenation, finally favoring EG production (58 %). When SnO was used, the catalyst promoted glucose isomerization, leading preferentially to PG (32 %). The above studies inspired our current work. A series of W and Ni-containing metal-organic frameworks were constructed by one-pot assembly of DUT-8(Ni) MOF precursors and Na2WO4·2H2O. A subsequent pyrolysis of the W@ DUT-8(Ni) materials at 700 °C under nitrogen produced nickel-tungsten/carbon catalysts. The following nomenclature was adopted for the resulting materials: NiW-l-x-C-N2; where x (nW/nNi) was set at 0.06, 0.12, 0.3, and 0.43, respectively. Figure 1 displays the catalytic results of the as-synthesized materials in the cellulose hydrogenolysis at 245 °C in a reaction time of 1 hour. Both materials with low (NiW-l-0.06-C-N2) and high (NiW-l-0.3-C-N2) W content were selective to EG (17 %). A remarkable yield switch to PG (36 %) was obtained at an average W loading (NiW-l-0.12-C-N2). The highest EG molar yield (25 %) was obtained over NiW-l-0.43-C-N2

A circadian clock is essential for homeostasis of group 3 innate lymphoid cells in the gut

International audienceGroup 3 innate lymphoid cells (ILC3) critically orchestrate host-microbe interactions in the healthy mammalian intestine and become substantially impaired in the context of inflammatory bowel disease (IBD). However, the molecular pathways controlling the homeostasis of ILC3 remain incompletely defined. Here, we identify that intestinal ILC3 are highly enriched in expression of genes involved in the circadian clock and exhibit diurnal oscillations of these pathways in response to light cues. Classical ILC3 effector functions also exhibited diurnal oscillations and lineage-specific deletion of BMAL1, a master regulator of the circadian clock, resulted in dramatically reduced ILC3s selectively in the intestine. BMAL1-deficient ILC3 exhibit impaired expression of Nr1d1 and Per3, hyper-activation of RORγt-dependent target genes, and elevated pro-apoptotic pathways. Depletion of the microbiota with antibiotics partially reduced the hyper-activation of BMAL1-deficient ILC3 and restored cellular homeostasis in the intestine. Finally, ILC3 isolated from the inflamed intestine of patients with IBD exhibit substantial alterations in expression of several circadian-related genes. Our results collectively define that circadian regulation is essential for the homeostasis of ILC3 in the presence of a complex intestinal microbiota, and further that this pathway is disrupted in the context of IBD

Tungsten carbides and nitrides supported on natural polymers-derived carbons for One-pot hydrogenolysis of cellulose to diols

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New insights on the catalytic reductive amination of hydroxyacetone amination over RUWXC/AC Catalyst

International audienceThe production of chemicals and liquid fuels from renewable and non-edible lignocellulosic biomass has been considered as a promising way to reduce our dependance to fossil resources as well as to reduce CO2 release. Especially, nitrogen-containing molecules, particularly primary amines, are broadly used for the synthesis of pharmaceuticals, polymers, surfactants, agrochemicals, and dyes[1]. Owing to the high O/C ratio (~1/1) in biomass feedstocks[2], the production of oxygenates from biomass is rather straightforward and has been largely studied. However, the further production of valuable nitrogen-containing products is far less evident due to the deficit of efficient amination strategies of oxygenates. One way is the amination of aldehydes and ketones to primary amines, employing ammonia as the nitrogen source[3]. Due to the development of biorefining, renewable aldehydes and ketones including glycolaldehyde, glyceraldehyde, hydroxyacetone, and aromatic compounds are nowadays available at large scales, opening new opportunities to produce nitrogen-containing compounds[4]. For example, Liang et al. reported the use of partly reduced Ru/ZrO2 for the reductive amination of different biomass-based aldehydes/ketones in aqueous ammonia[5]. Despite this encouraging development, effective heterogeneous catalytic systems that allow the amination reaction to take place under milder conditions (T < 100 °C, P < 50 bar, aqueous phase, and without additives) with high amines’ yields are still lacking. In particular, the production of large-market amino alcohols from hydroxyacetone hasn’t been reported so far.Herein, we report the preparation of a highly efficient and robust catalyst, RuWxC/AC, for the reductive amination of hydroxyacetone (Figure 1). By varying several process parameters including time, temperature, the nature of nitrogen source, and pressure, up to 60 mol.% amines’ yield has been obtained. The promoting effect of tungsten carbide nanoparticles has been particularly investigated. Finally, a kinetic study has been conducted and will be discussed

Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2

International audienceInterleukin (IL)-2 is a pleiotropic cytokine that is necessary to prevent chronic inflammation in the gastrointestinal tract 1-4. The protective effects of IL-2 involve the generation, maintenance and function of regulatory T (T reg) cells 4-8 , and the use of low doses of IL-2 has emerged as a potential therapeutic strategy for patients with inflammatory bowel disease 9. However, the cellular and molecular pathways that control the production of IL-2 in the context of intestinal health are undefined. Here we show, in a mouse model, that IL-2 is acutely required to maintain T reg cells and immunological homeostasis throughout the gastrointestinal tract. Notably, lineage-specific deletion of IL-2 in T cells did not reduce T reg cells in the small intestine. Unbiased analyses revealed that, in the small intestine, group-3 innate lymphoid cells (ILC3s) are the dominant cellular source of IL-2, which is induced selectively by IL-1β. Macrophages in the small intestine produce IL-1β, and activation of this pathway involves MYD88-and NOD2-dependent sensing of the microbiota. Our loss-of-function studies show that ILC3-derived IL-2 is essential for maintaining T reg cells, immunological homeostasis and oral tolerance to dietary antigens in the small intestine. Furthermore, production of IL-2 by ILC3s was significantly reduced in the small intestine of patients with Crohn's disease, and this correlated with lower frequencies of T reg cells. Our results reveal a previously unappreciated pathway in which a microbiota-and IL-1β-dependent axis promotes the production of IL-2 by ILC3s to orchestrate immune regulation in the intestine. To determine whether IL-2 is constitutively required for the maintenance of T reg cells and immunological homeostasis in the intestine, we administered isotype-control or anti-IL-2 neutralizing antibodies every other day to adult mice for two weeks. Within this short time period, the neutralization of IL-2 promoted an enlargement of the spleen and mesenteric lymph nodes, and caused significant reductions of T reg cells and significant increases in the proliferation of CD4 + T cells throughout the gastrointestinal tract and associated lymphoid tissues, including the mesenteric lymph nodes, large intestine and small intestine (Extended Data Fig. 1a-g). Blockade of IL-2 resulted in significantly enhanced IFNγ production by CD4 + T cells in both the small and large intestine, as well as increased IL-17A production in the large intestine (Extended Data Fig. 1h-k). Previous studies have suggested that CD4 + T cells are the dominant cellular source of IL-2 1,2. Therefore, we generated mice with a lineage-specific deletion of IL-2 in T cells by crossing IL-2-floxed mice 10 with Lck cre mice. Lck cre Il2 f/f mice exhibited a complete loss of IL-2 protein staining in T cells, and we observed a significant reduction in the number of T reg cells, and an increase in CD4 + T cell proliferation and effector function in the mesenteric lymph nodes and large intestine (Extended Data Fig. 2a-g). By contrast, deletion o