IgG and Fcγ Receptors in Intestinal Immunity and Inflammation.

Fcγ receptors (FcγR) are cell surface glycoproteins that mediate cellular effector functions of immunoglobulin G (IgG) antibodies. Genetic variation in FcγR genes can influence susceptibility to a variety of antibody-mediated autoimmune and inflammatory disorders, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). More recently, however, genetic studies have implicated altered FcγR signaling in the pathogenesis of inflammatory bowel disease (IBD), a condition classically associated with dysregulated innate and T cell immunity. Specifically, a variant of the activating receptor, FcγRIIA, with low affinity for IgG, confers protection against the development of ulcerative colitis, a subset of IBD, leading to a re-evaluation of the role of IgG and FcγRs in gastrointestinal tract immunity, an organ system traditionally associated with IgA. In this review, we summarize our current understanding of IgG and FcγR function at this unique host-environment interface, from the pathogenesis of colitis and defense against enteropathogens, its contribution to maternal-fetal cross-talk and susceptibility to cancer. Finally, we discuss the therapeutic implications of this information, both in terms of how FcγR signaling pathways may be targeted for the treatment of IBD and how FcγR engagement may influence the efficacy of therapeutic monoclonal antibodies in IBD

ATLAS ITk Short Strip Prototype Module with Integrated DCDC Powering and Control Phase II Upgrade of the ATLAS Inner Tracker detector at the HL - LHC

The prototype Barrel module design, for the Phase II upgrade of the of the new Inner Tracker (ITk) detector at the LHC, has adopted an integrated low mass assembly featuring single-sided flexible circuits, with readout ASICs, glued to the silicon strip sensor. Further integration has been achieved by the attachment of module DCDC powering, HV sensor biasing switch and autonomous monitoring and control to the sensor. This low mass, integrated module approach benefits further in a reduced width stave structure to which the modules are attached. The results of preliminary electrical tests of such an integrated module will be presented

Mesenchymal stem cells engineered to express selectin ligands and IL-10 exert enhanced therapeutic efficacy in murine experimental autoimmune encephalomyelitis.

Systemic administration of mesenchymal stem cells (MSCs) affords the potential to ameliorate the symptoms of Multiple Sclerosis (MS) in both preclinical and clinical studies. However, the efficacy of MSC-based therapy for MS likely depends on the number of cells that home to inflamed tissues and on the controlled production of paracrine and immunomodulatory factors. Previously, we reported that engineered MSCs expressing P-selectin glycoprotein ligand-1 (PSGL-1) and Sialyl-Lewis(x) (SLeX) via mRNA transfection facilitated the targeted delivery of anti-inflammatory cytokine interleukin-10 (IL-10) to inflamed ear. Here, we evaluated whether targeted delivery of MSCs with triple PSGL1/SLeX/IL-10 engineering improves therapeutic outcomes in mouse experimental autoimmune encephalomyelitis (EAE), a murine model for human MS. We found PSGL-1/SLeX mRNA transfection significantly enhanced MSC homing to the inflamed spinal cord. This is consistent with results from in vitro flow chamber assays in which PSGL-1/SleX mRNA transfection significantly increased the percentage of rolling and adherent cells on activated brain microvascular endothelial cells, which mimic the inflamed endothelium of blood brain/spinal cord barrier in EAE. In addition, IL-10-transfected MSCs show significant inhibitory activity on the proliferation of CD4(+) T lymphocytes from EAE mice. In vivo treatment with MSCs engineered with PSGL-1/SLeX/IL-10 in EAE mice exhibited a superior therapeutic function over native (unmodified) MSCs, evidenced by significantly improved myelination and decreased lymphocytes infiltration into the white matter of the spinal cord. Our strategy of targeted delivery of performance-enhanced MSCs could potentially be utilized to increase the effectiveness of MSC-based therapy for MS and other central nervous system (CNS) disorders

Additional file 1: Figure S1. of Exogenous marker-engineered mesenchymal stem cells detect cancer and metastases in a simple blood assay

Firefly and humanized Gaussia luciferases are substrate-specific and not cross-reactive. hGluc-MSCs, Fluc-tdT-MSCs (Fluc-MSCs), and N-MSCs were seeded in 96-well plate. The firefly luciferase substrate D-luciferin (final concentration = 150 μg/ml) or the humanized Gaussia luciferase substrate CTZ (final concentration = 20 μM) was added, and luciferase activity was measured with a plate reader. Error bar: mean ± standard deviation. Exposure time = 2 s. A.U. arbitrary units, CTZ coelenterazine, Fluc firefly luciferase, hGluc humanized Gaussia luciferase, MSC mesenchymal stem cell, tdT tdTomato red fluorescent protein. (PNG 37 kb