The transcriptional repressor Bcl6 controls the stability of regulatory T cells by intrinsic and extrinsic pathways

Foxp3(+) regulatory T (Treg) cells are essential to maintain immune homeostasis, yet controversy exists about the stability of this cell population. Bcl6-deficient (Bcl6(-/-) ) mice develop severe and spontaneous T helper type 2 (Th2) inflammation and Bcl6-deficient Treg cells are ineffective at controlling Th2 responses. We used a lineage tracing approach to analyse the fate of Treg cells in these mice. In the periphery of Bcl6(-/-) mice, increased numbers of Foxp3-negative 'exTreg' cells were found, particularly in the CD25(+) population. ExTreg cells from Bcl6(-/-) mice expressed increased interleukin-17 (IL-17) and extremely elevated levels of Th2 cytokines compared with wild-type exTreg cells. Although Treg cells normally express only low levels of cytokines, Treg cells from Bcl6(-/-) mice secreted higher levels of IL-4, IL-5, IL-13 and IL-17 than wild-type conventional T cells. Next, Treg-specific conditional Bcl6-deficient (Bcl6(Foxp3-/-) ) mice were analysed. Bcl6(Foxp3-/-) mice do not develop inflammatory disease, indicating a requirement for non-Treg cells for inflammation in Bcl6(-/-) mice, and have normal numbers of exTreg cells. We induced Th2-type allergic airway inflammation in Bcl6(Foxp3-/-) mice, and found that while exTreg cytokine expression was normal, Bcl6-deficient Treg cells expressed higher levels of the Th2-specific regulator Gata3 than Bcl6(+) Treg cells. Bcl6(Foxp3-/-) mice had increased numbers of Th2 cells after induction of airway inflammation and increased T cells in the bronchoalveolar lavage fluid. These data show both Treg-intrinsic and Treg-extrinsic roles for Bcl6 in controlling Treg cell stability and Th2 inflammation, and support the idea that Bcl6 expression in Treg cells is critical for controlling Th2 responses

Serum MicroRNA-21 as a Biomarker for Allergic Inflammatory Disease in Children

MicroRNAs (miRs) have emerged as useful biomarkers for different disease states, including allergic inflammatory diseases such as asthma and eosinophilic esophagitis (EoE). Serum miRs are a possible non-invasive method for diagnosis of such diseases. We focused on microRNA-21 (miR-21) levels in serum, in order to assess the feasibility of using this gene as a non-invasive biomarker for these diseases in the clinic, as well as to better understand the expression pattern of miR-21 in allergic inflammation. We used quantitative PCR (QPCR) to assay miR-21 and other control miRs in esophageal biopsies from EoE patients and serum samples from EoE and asthma patients. Serum levels of miR-21 were significantly elevated in patients with asthma, whereas serum miR-21 levels were not associated with the presence of allergen-specific IgE (i.e. atopy). Esophageal biopsies showed a large elevation of miR-21 in EoE and an increase in miR-21 in EoE serum. Control U6 miR did not vary between asthma and control patients, however EoE serum had significantly decreased U6 microRNA compared to controls. The decreased U6 in EoE sera did not completely account for the relative increase in miR-21 in the sera of EoE patients. We report for the first time that miR-21 is elevated in the sera of both asthma and EoE patients. We find no relation between serum miR-21 levels and atopy. Our results thus suggest miR-21 is a novel biomarker for human allergic inflammatory diseases

MesonNet 2013 International Workshop. Mini-proceedings

The mini-proceedings of the MesonNet 2013 International Workshop held in Prague from June 17th to 19th, 2013, are presented. MesonNet is a research network within EU HadronPhysics3 project (1/2012 -- 12/2014). The web page of the conference, which contains all talks, can be found at http://ipnp.mff.cuni.cz/mesonnet13Comment: 106 pages, 53 contributions. Mini-proceedings of the MesonNet 2013 International Workshop. Editors: K. Kampf, A. Kupsc, and P. Masjua

Search for eta-mesic 4He in the dd->3He n pi0 and dd->3He p pi- reactions with the WASA-at-COSY facility

The search for 4He-eta bound states was performed with the WASA-at-COSY facility via the measurement of the excitation function for the dd->3He n pi0 and dd->3He p pi- processes. The beam momentum was varied continuously between 2.127 GeV/c and 2.422 GeV/c, corresponding to the excess energy for the dd->4He eta reaction ranging from Q=-70 MeV to Q=30 MeV. The luminosity was determined based on the dd->3He n reaction and quasi-free proton-proton scattering via dd->pp n_spectator n_spectator reactions. The excitation functions determined independently for the measured reactions do not reveal a structure which could be interpreted as a narrow mesic nucleus. Therefore, the upper limits of the total cross sections for the bound state production and decay in dd->(4He-eta)_bound->3He n pi0 and dd->(4He-eta)_bound->3He p pi- processes were determined taking into account the isospin relation between both the channels considered. The results of the analysis depend on the assumptions of the N* momentum distribution in the anticipated mesic-4He. Assuming as in the previous works, that this is identical with the distribution of nucleons bound with 20 MeV in 4He, we determined that (for the mesic bound state width in the range from 5 MeV to 50 MeV) the upper limits at 90% confidence level are about 3 nb and about 6 nb for npi0 and ppi- channels, respectively. However, based on the recent theoretical findings of the N*(1535) momentum distribution in the N*-3He nucleus bound by 3.6 MeV, we find that the WASA-at-COSY detector acceptance decreases and hence the corresponding upper limits are 5 nb and 10 nb for npi0 and ppi- channels respectively.Comment: This article will be submitted to JHE

Neutron-Proton Scattering in the Context of the d∗d^*(2380) Resonance

New data on quasifree polarized neutron-proton scattering, in the region of the recently observed $d^*$ resonance structure, have been obtained by exclusive and kinematically complete high-statistics measurements with WASA at COSY. This paper details the determination of the beam polarization, checks of the quasifree character of the scattering process, on all obtained $A_y$ angular distributions and on the new partial-wave analysis, which includes the new data producing a resonance pole in the $^3D_3$-$^3G_3$ coupled partial waves at ($2380\pm10 - i40\pm5$) MeV -- in accordance with the $d^*$ dibaryon resonance hypothesis. The effect of the new partial-wave solution on the description of total and differential cross section data as well as specific combinations of spin-correlation and spin-transfer observables available from COSY-ANKE measurements at $T_d$ = 2.27 GeV is discussed

Charge Symmetry Breaking in dd->4He{\pi}0 with WASA-at-COSY

Charge symmetry breaking (CSB) observables are a suitable experimental tool to examine effects induced by quark masses on the nuclear level. Previous high precision data from TRIUMF and IUCF are currently used to develop a consistent description of CSB within the framework of chiral perturbation theory. In this work the experimental studies on the reaction dd->4He{\pi}0 have been extended towards higher excess energies in order to provide information on the contribution of p-waves in the final state. For this, an exclusive measurement has been carried out at a beam momentum of p=1.2 GeV/c using the WASA-at-COSY facility. The total cross section amounts to sigma(tot) = (118 +- 18(stat) +- 13(sys) +- 8(ext)) pb and first data on the differential cross section are consistent with s-wave pion production.Comment: 14 pages, 5 figure

ABC Effect and Resonance Structure in the Double-Pionic Fusion to 3^3He

Exclusive and kinematically complete measurements of the double pionic fusion to $^3$He have been performed in the energy region of the so-called ABC effect, which denotes a pronounced low-mass enhancement in the $\pi\pi$-invariant mass spectrum. The experiments were carried out with the WASA detector setup at COSY. Similar to the observations in the basic $pn \to d \pi^0\pi^0$ reaction and in the $dd \to ^4$He$\pi^0\pi^0$ reaction, the data reveal a correlation between the ABC effect and a resonance-like energy dependence in the total cross section. Differential cross sections are well described by the hypothesis of $d^*$ resonance formation during the reaction process in addition to the conventional $t$-channel $\Delta\Delta$ mechanism. The deduced $d^*$ resonance width can be understood from collision broadening due to Fermi motion of the nucleons in initial and final nuclei

Search for the eta-mesic 4He with WASA-at-COSY detector

An exclusive measurement of the excitation function for the dd->3Heppi- reaction was performed at the Cooler Synchrotron COSY-Juelich with the WASA-at-COSY detection system. The data were taken during a slow acceleration of the beam from 2.185 GeV/c to 2.400 GeV/c crossing the kinematic threshold for the eta meson production in the dd->4He-eta reaction at 2.336 GeV/c. The corresponding excess energy with respect to the 4He-eta system varied from -51.4MeV to 22MeV. The integrated luminosity in the experiment was determined using the dd->3Hen reaction. The shape of the excitation function for the dd->3Heppi- was examined. No signal of the 4He-eta bound state was observed. An upper limit for the cross-section for the bound state formation and decay in the process dd->(4He-eta)bound->3Heppi- was determined on the 90% confidence level and it varies from 20nb to 27nb for the bound state width ranging from 5MeV to 35MeV, respectively.Comment: 8 pages, 9 figure