CD4CD8αα Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease

It has become evident that bacteria in our gut affect health and disease, but less is known about how they do this. Recent studies in mice showed that gut Clostridium bacteria and their metabolites can activate regulatory T cells (Treg) that in turn mediate tolerance to signals that would ordinarily cause inflammation. In this study we identify a subset of human T lymphocytes, designated CD4CD8αα T cells that are present in the surface lining of the colon and in the blood. We demonstrate Treg activity and show these cells to be activated by microbiota; we identify F. prausnitzii, a core Clostridium strain of the human gut microbiota, as a major inducer of these Treg cells. Interestingly, there are fewer F. prausnitzii in individuals suffering from inflammatory bowel disease (IBD), and accordingly the CD4CD8αα T cells are decreased in the blood and gut of patients with IBD. We argue that CD4CD8αα colonic Treg probably help control or prevent IBD. These data open the road to new diagnostic and therapeutic strategies for the management of IBD and provide new tools to address the impact of the intestinal microbiota on the human immune system

ARCHITECTURES MULTIMÉTALLIQUES FONCTIONNELLES : COMPORTEMENT DE MOLECULE-AIMANT ET PHOTO-MAGNETISME

This work focuses on the synthesis of discrete molecules showing bifunctionality based on single-molecule magnet behavior or photo-switchable processes. The first part of this work concerns information storage at the molecular scale via the synthesis of anisotropic high spin compounds showing a single-molecule magnet behavior. New compounds (CoMn6, CrMn6, S = 21/2) have been obtained showing the important role of the control of intermolecular interactions. Particular attention has been paid to the design of multifunctional supramolecular architectures bearing three or four different metal ions. Using the strategy « polynuclear complexes as ligand », new families of compounds have been developed, exhibiting different topologies such as derivatives of CoTbCu complexes or hetero-tetra-metallic compounds (i.e. MoCuTb-Ni). The second part of this work is devoted to the synthesis of photomagnetic « Molybdenum-Copper » complexes. The synthesis of model compounds, MoZn2 and MoZn0.95Cu0.05, and the study of the photo-induced metastable states enabled a better understanding or the photomagnetic behavior. Thus, a spin transition on the molybdenum center and a photo-induced electron transfer from the molybdenum to the copper has been demonstrated. Higher nuclearity compounds have also been obtained, Mo3Cu4 and Mo6Cu13. Finally, the deposition of photo-magnetic molecules on surface as also been carried out using Langmuir-Blodgett technique.Ce travail de thèse a consisté en l’élaboration et l’étude de molécules montrant une bifonctionnalité basée sur un comportement de molécule-aimant ou sur des effets de commutation au sein de complexes photo-magnétiques de type « Molybdène-Cuivre ». La synthèse de composés modèles MoZn2 et MoZn0.95Cu0.05 et l’étude des états photo-induits a conduit à la démonstration de deux phénomènes sous irradiation : effet LIESST (transition de spin) sur le Mo(IV) et transfert d’électron dans des composés MoCu. Des composés photo-actifs de plus haute nucléarité ont également été obtenus, Mo3Cu4 et Mo6Cu13. Enfin, le dépôt sur surface de molécules photo-magnétiques a été réalisé via la technique Langmuir-Blodgett.La seconde partie du travail s’est intéressée au stockage de l’information à l’échelle moléculaire via la synthèse de composés à haut spin anisotropes ayant un comportement de molécule-aimant. En ce sens, de nouveaux composés (CoMn6, CrMn6, S = 21/2) ont été synthétisés mettant en évidence le caractère crucial du contrôle des interactions intermoléculaires. Un intérêt particulier a été porté à l’élaboration d’architectures supramoléculaires multifonctionnelles comportant trois ou quatre métaux différents. En utilisant la stratégie de synthèse « complexe polynucléaire comme ligand », de nouvelles familles de composés ont été développées, de différentes topologies, comme des dérivés à base de CoTbCu et une large famille de complexes hétéro-tétra-métalliques (i.e. MoCuTb-Ni)

Architectures multimétalliques fonctionnelles (comportement de molécule-aimant et photo-magnétisme)

L objectif de ce travail est d obtenir des molécules discrètes montrant une bifonctionnalité basée sur un comportement de molécule-aimant ou des effets de photo-commutation. Une première partie de la thèse s intéresse au stockage de l information à l échelle moléculaire via la synthèse de composés à haut spin anisotropes ayant un comportement de molécule-aimant. En ce sens, de nouveaux composés (CoMn6, CrMn6, S = 21/2) ont été synthétisés mettant en évidence le caractère crucial du contrôle des interactions intermoléculaires. Un intérêt particulier a été porté à l élaboration d architectures supramoléculaires multifonctionnelles comportant trois ou quatre métaux différents. En utilisant la stratégie de synthèse complexe polynucléaire comme ligand , de nouvelles familles de composés ont été développées, de différentes topologies, comme des dérivés à base de CoTbCu et des complexes hétéro-tétra-métalliques (i.e. MoCuTb-Ni). La seconde partie du travail s est focalisé sur l obtention de complexes photomagnétiques de type Molybdène-Cuivre . La synthèse de composés modèles MoZn2 et MoZn0.95Cu0.05 et l étude des états photo-induits a permis une meilleure compréhension du comportement photomagnétique. Ainsi, une transition de spin centrée sur le molybdène et un transfert d électron photo-induit du molybdène au cuivre ont été mis en évidence. Des composés de plus haute nucléarité ont également été obtenus, Mo3Cu4 et Mo6Cu13. Enfin, le dépôt sur surface de molécules photo-magnétiques a été réalisé via la technique Langmuir-Blodgett.This work focuses on the synthesis of discrete molecules showing bifunctionality based on single-molecule magnet behavior or photo-switchable processes. The first part of this work concerns information storage at the molecular scale via the synthesis of anisotropic high spin compounds displaying a single-molecule magnet behavior. New compounds (CoMn6, CrMn6, S = 21/2) have been obtained showing the important role of the control of intermolecular interactions. Particular attention has been paid to the design of multifunctional supramolecular architectures bearing three or four different metal ions. Using the strategy polynuclear complexes as ligand , new families of compounds have been developed, exhibiting different topologies such as derivatives of CoTbCu complexes or hetero-tetra-metallic compounds (i.e. MoCuTb-Ni). The second part of this work is devoted to the synthesis of photomagnetic Molybdenum-Copper complexes. The synthesis of model compounds, MoZn2 and MoZn0.95Cu0.05, and the study of the photo-induced metastable states enabled a better understanding of the photomagnetic behavior. Thus, a spin transition on the molybdenum center and a photo-induced electron transfer from the molybdenum to the copper has been demonstrated. Higher nuclearity compounds have also been obtained, Mo3Cu4 and Mo6Cu13. Finally, the deposition of photo-magnetic molecules on surface as also been carried out using Langmuir-Blodgett technique.PARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Stereoisomerism in Tetrametallic Propeller‐Like Complexes: A Solid‐State and Solution NMR Study on a Tetragallium(III) Derivative

International audienceTetragallium(III) complex in [Ga4(L4-Py)2(dpm)6] ⋅ EtOH, with H3L4-Py=2-(hydroxymethyl)-2-(pyridin-4-yl)propane-1,3-diol and Hdpm=dipivaloylmethane, was investigated as a diamagnetic analogue of tetrametallic, propeller-like single-molecule magnets (SMMs). The chiral molecular structure partitions the six CH2 protons of each tripodal (L4-Py)3− ligand into two diastereotopic sets. The two signals were clearly detected by 1H NMR spectroscopy in C6D6, proving that Λ and Δ enantiomers interconvert slowly over NMR timescale. Density functional theory calculations provided quantitative agreement with the observed values of chemical shifts and scalar coupling constants across both geminal and long-range interaction pathways. The solid-state structure suggests the occurrence of a lower symmetry stereoisomer (27 mol%), which was clearly identified in the NMR spectra. Since high spin Fe3+ forms distinctly more inert complexes than Ga3+, comparable or greater configurational stability is expected for the isostructural FeIII4, FeIII3CrIII, and FeIII3VIII SMMs, which are difficult to investigate by solution NMR because of the strong paramagnetism

A new versatile class of hetero-tetra-metallic assemblies: highlighting single-molecule magnet behaviour

International audienceHetero-tetra-metallic species based on hexanuclear assemblies [((valen)M1)Ln(OH2)2(μM2(CN)8)]22− (Ln = GdIII, TbIII; M1 = CuII, NiII and M2 = MoIV, WIV) and co-crystallized mononuclear complexes [M3(tpy)2]2+ (M3 = NiII, RuII, OsII) were identified, fully characterized, and shown to constitute a new class of single-molecule magnets

Evidence of crystal packing effects in stabilizing high or low spin states of iron(II) complexes with functionalized 2,6-bis(pyrazol-1-yl)pyridine ligands

The molecular structures and magnetic properties of homoleptic iron(II) compounds [Fe(bpp-COOMe)2](ClO4)2 (1) and [Fe(bpp-triolH3)2](ClO4)2 (2) have been investigated to ascertain their spin crossover (SCO) behaviour. In these hexacoordinated complexes, the bpp (2,6-bis(pyrazol-1-yl)pyridine) ligands adopt a mer-mer coordination mode and carry COOMe or C(O)NHC(CH2OH)3 para substituents, respectively, on the central pyridyl ring. In spite of the almost equal donor power of the ligands to the iron(II) centre, the two compounds feature different spin state configurations at room temperature. Compound 1 displays a highly-distorted octahedral environment around the iron(II) centre, which adopts a high spin (HS) state at all temperatures, even under an external applied pressure up to 1.0 GPa. By contrast, 2 is characterized by a more regular octahedral coordination around the metal ion and exhibits a low spin (LS) configuration at or below room temperature. However, it shows a thermally-induced SCO behaviour at T > 400 K, along with Light-Induced Excited Spin State Trapping (LIESST) at low temperature, with TLIESST = 38 K. Since DFT (U)M06/6-311+G(d) geometry optimizations in vacuo indicate that both complexes should adopt a HS state and a highly-distorted coordination geometry, the stabilization of a LS configuration in 2 is ultimately ascribed to the effect of intermolecular hydrogen bonds, which align the [Fe(bpp-triolH3)2]2+ cations in 1D chains and impart profound differences in the geometric arrangement of the ligands

Photomagnetic molecular and extended network Langmuir-Blodgett films based on cyanide bridged Molybdenum-Copper complexes.

International audienc

Faecal D/L lactate ratio is a metabolic signature of microbiota imbalance in patients with short bowel syndrome

Our objective was to understand the functional link between the composition of faecal microbiota and the clinical characteristics of adults with short bowel syndrome (SBS). Sixteen patients suffering from type II SBS were included in the study. They displayed a total oral intake of 2661 +/- 1005 Kcal/day with superior sugar absorption (83 +/- 12%) than protein (42 +/- 13%) or fat (39 +/- 26%). These patients displayed a marked dysbiosis in faecal microbiota, with a predominance of Lactobacillus/Leuconostoc group, while Clostridium and Bacteroides were under-represented. Each patient exhibited a diverse lactic acid bacteria composition (L. delbrueckii subsp. bulgaricus, L. crispatus, L. gasseri, L. johnsonii, L. reuteri, L. mucosae), displaying specific D and L-lactate production profiles in vitro. Of 16 patients, 9/16 (56%) accumulated lactates in their faecal samples, from 2 to 110 mM of D-lactate and from 2 to 80 mM of L-lactate. The presence of lactates in faeces (56% patients) was used to define the Lactate-accumulator group (LA), while absence of faecal lactates (44% patients) defines the Non lactate-accumulator group (NLA). The LA group had a lower plasma HCO3(-) concentration (17.1 +/- 2.8 mM) than the NLA group (22.8 +/- 4.6 mM), indicating that LA and NLA groups are clinically relevant sub-types. Two patients, belonging to the LA group and who particularly accumulated faecal D-lactate, were at risk of D-encephalopathic reactions. Furthermore, all patients of the NLA group and those accumulating preferentially L isoform in the LA group had never developed D-acidosis. The D/L faecal lactate ratio seems to be the most relevant index for a higher D-encephalopathy risk, rather than D-and L-lactate faecal concentrations per se. Testing criteria that take into account HCO3(-) value, total faecal lactate and the faecal D/L lactate ratio may become useful tools for identifying SBS patients at risk for D-encephalopathy

Direct Synthesis of Mesoionic Carbene (MIC) Stabilized Gold Nanoparticles from 1,2,3-Triazolium Salts

Significant achievements have been reported in the last few years regarding the stabilization and functionalisation of gold nanoparticles (AuNPs), mainly through the use of thiols and imidazolylidene N-heterocyclic carbenes capping ligands. Herein, we report that mesoionic carbenes (MICs) ligands, based on the 1,2,3-triazol-5-ylidene scaffold, allow the expeditive preparation of AuNPs of exceptional stability through a simple and straightforward one-pot protocol directly from triazolium salts and discrete Au(III) sources. Control over the size of the AuNPs has been achieved by varying the Au/ligand ratio as well as the nature of the triazolium salts, the latter being facilitated by the ease of synthesis of the MIC precursors through click chemistry. Characterisation of these MIC-AuNPs by X-ray photoelectron spectroscopy (XPS) hints at the exclusive presence of MICs on the nanoparticle surface

First evidence of light-induced spin transition in molybdenum (IV)

Photo-induced spin transition in a molybdenum-zinc complex has been evidenced and fully characterized by Squid magnetometry and several spectroscopies performed under irradiation (IR, EPR, etc.). The phenomenon has been confirmed by X-ray diffraction and DFT calculations yielding a Light-Induced Excited Spin State Trapping Effect (LIESST) on a 4d transition metal ion