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Interleukin-23 (IL-23) responsive group 3 innate lymphoid cells (ILC3s) have been implicated in immune homeostasis and pathogenesis in the adult, but little is known about their roles in the newborn. Here we show that IL-23 promotes conversion of embryonic intestinal Lin−IL-23R+Thy1+ cells into IL-22-producing Thy1+Sca-1hi ILC3s in vitro. Gut-specific expression of IL-23 also activated and expanded Thy1+Sca-1hi ILC3s, which produced IL-22, IL-17, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) and were distinct from canonical CD4+ lymphoid tissue inducer (LTi) cells. These ILC3s accumulated under the epithelium in intercellular adhesion molecule (ICAM)-1-positive cell aggregates together with neutrophils that disrupted the epithelium, leading to the formation of discrete intestinal erosions, bleeding, and neonatal death. Genetic and antibody depletion of ILC3s rescued the mice from neonatal death. Antibiotic treatment of pregnant mothers and offspring prolonged survival of IL-23 transgenic mice, suggesting a role for the commensal flora on ILC3-induced pathogenesis. Our results reveal a novel role for the IL-23–ILC3s axis in the pathogenesis of neonatal intestinal inflammation.

Myeloid-derived suppressor cells (MDSC) are myeloid cells that suppress the immune response, a definition that reflects both their origin and their function. As negative regulators of the immune response, MDSC represent a novel therapeutic approach for manipulating the immune system toward tolerance or immunity. MDSC are present in cancer patients and tumor-bearing mice and are in part responsible for the inhibition of the cell-mediated immune response against the tumor. Our laboratories investigate the immunologic mechanisms of tumor acceptance mediated by MDSC, which can be exploited to prevent allograft rejection in transplantation. A better understanding of MDSC biology will open new avenues for therapeutic intervention, either by inhibiting their function (i.e. in cancer patients), or by enhancing their suppressive effects and promoting their expansion (i.e. in organ transplantation and alloimmune responses). In this review, we summarize some of the critical aspects of the immunoregulatory function of MDSC in cancer and transplantation and discuss their potential clinical applications.

One of the main unresolved questions in solid organ transplantation is how to establish indefinite graft survival that is free from long-term treatment with immunosuppressive drugs and chronic rejection (i.e., the establishment of tolerance). The failure to achieve this goal may be related to the difficulty in identifying the phenotype and function of the cell subsets that participate in the induction of tolerance. To address this issue, we investigated the suppressive roles of recipient myeloid cells that may be manipulated to induce tolerance to transplanted hearts in mice. Using depleting mAbs, clodronate-loaded liposomes, and transgenic mice specific for depletion of CD11c+, CD11b+, or CD115+ cells, we identified a tolerogenic role for CD11b+CD115+Gr1+ monocytes during the induction of tolerance by costimulatory blockade with CD40L-specific mAb. Early after transplantation, Gr1+ monocytes migrated from the bone marrow into the transplanted organ, where they prevented the initiation of adaptive immune responses that lead to allograft rejection and participated in the development of Tregs. Our results suggest that mobilization of bone marrow CD11b+CD115+Gr1+ monocytes under sterile inflammatory conditions mediates the induction of indefinite allograft survival. We propose that manipulating the common bone marrow monocyte progenitor could be a useful clinical therapeutic approach for inducing transplantation tolerance.

Lot of efforts have been devoted by ATLAS and CMS teams to improve the quality of LHC events analysis with the Matrix Element Method (MEM). Up to now, very few implementations try to face up the huge computing resources required by this method. We propose here a highly parallel version, combining MPI and OpenCL, which makes the MEM exploitation reachable for the whole CMS datasets with a moderate cost. In the article, we describe the status of two software projects under development, one focused on physics and one focused on computing. We also showcase their preliminary performance obtained with classical multi-core processors, CUDA accelerators and MIC co-processors. This let us extrapolate that with the help of 6 high-end accelerators, we should be able to reprocess the whole LHC run 1 within 10 days, and that we have a satisfying metric for the upcoming run 2. The future work will consist in finalizing a single merged system including all the physics and all the parallelism infrastructure, thus optimizing implementation for best hardware platforms.

The induction of alloantigen-specific unresponsiveness remains an elusive goal in organ transplantation. Here we identify plasmacytoid dendritic cells (pDCs) as phagocytic antigen-presenting cells essential for tolerance to vascularized cardiac allografts. Tolerizing pDCs acquired alloantigen in the allograft and then moved through the blood to home to peripheral lymph nodes. In the lymph node, alloantigen-presenting pDCs induced the generation of CCR4 + CD4 + CD25 + Foxp3 + regulatory T cells (T reg cells). Depletion of pDCs or prevention of pDC lymph node homing inhibited peripheral T reg cell development and tolerance induction, whereas adoptive transfer of tolerized pDCs induced T reg cell development and prolonged graft survival. Thus, alloantigen-presenting pDCs home to the lymph nodes in tolerogenic conditions, where they mediate alloantigen-specific T reg cell development and allograft tolerance.

A measurement of the ttbar production cross section at sqrt(s)=13 TeV is presented using proton-proton collisions, corresponding to an integrated luminosity of 2.3 inverse femtobarns, collected with the CMS detector at the LHC. Final states with one isolated charged lepton (electron or muon) and at least one jet are selected and categorized according to the accompanying jet multiplicity. From a likelihood fit to the invariant mass distribution of the isolated lepton and a jet identified as coming from the hadronization of a bottom quark, the cross section is measured to be sigma(ttbar)= 835 +/- 3 (stat) +/- 23 (syst) +/- 23 (lum) pb, in agreement with the standard model prediction. Using the expected dependence of the cross section on the pole mass of the top quark (m[t]), the value of m[t] is found to be 172.7+2.4-2.7 GeV.

The results of a first search for CP violation in the production and decay of top quark-antiquark (ttbar) pairs are presented. The search is based on asymmetries in T-odd, triple-product correlation observables, where T is the time-reversal operator. The analysis uses a sample of proton-proton collisions at sqrt(s)=8 TeV collected by the CMS experiment, corresponding to an integrated luminosity of 19.7 inverse femtobarns.. Events are selected having one electron or muon and at least four jets. The T-odd observables are measured using four-momentum vectors associated with ttbar production and decay. The measured asymmetries exhibit no evidence for CP-violating effects, consistent with the expectation from the standard model.

This paper describes the search for a high-mass narrow-width scalar particle decaying into a Z boson and a photon. The analysis is performed using proton-proton collision data recorded with the CMS detector at the LHC at center-of-mass energies of 8 and 13 TeV, corresponding to integrated luminosities of 19.7 and 2.7 inverse femtobarns, respectively. The Z bosons are reconstructed from opposite-sign electron or muon pairs. No statistically significant deviation from the standard model predictions has been found in the 200-2000 GeV mass range. Upper limits at 95% confidence level have been derived on the product of the scalar particle production cross section and the branching fraction of the Z decaying into electrons or muons, which range from 280 to 20 fb for resonance masses between 200 and 2000 GeV.

This paper reports the measurement of J/psi meson production in proton-proton (pp) and proton-lead (pPb) collisions at a center-of-mass energy per nucleon pair of 5.02 TeV by the CMS experiment at the LHC. The data samples used in the analysis correspond to integrated luminosities of 28 inverse picobarns and 35 inverse nanobarns for pp and pPb collisions, respectively. Prompt and nonprompt J/psi mesons, the latter issuing from the decay of B mesons, are measured in their dimuon decay channels. Differential cross sections are measured in the transverse momentum range of 2

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