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Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive err…
2020
Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects …
Tracking zoonotic pathogens using blood-sucking flies as 'flying syringes'
2017
About 60% of emerging infectious diseases in humans are of zoonotic origin. Their increasing number requires the development of new methods for early detection and monitoring of infectious agents in wildlife. Here, we investigated whether blood meals from hematophagous flies could be used to identify the infectious agents circulating in wild vertebrates. To this aim, 1230 blood-engorged flies were caught in the forests of Gabon. Identified blood meals (30%) were from 20 vertebrate species including mammals, birds and reptiles. Among them, 9% were infected by different extant malaria parasites among which some belonged to known parasite species, others to new parasite species or to parasite …
Phosphorylated immunoreceptor tyrosine-based activation motifs and integrin cytoplasmic domains activate spleen tyrosine kinase via distinct mechanis…
2018
Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated immunoreceptor tyrosine-based activation motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues. In addition to its immunoreceptor function, Syk is activated downstream of integrin pathways, and integrins bind to the same region in Syk a…
Immunosenescence and its hallmarks: How to oppose aging strategically? A review of potential options for therapeutic intervention
2019
Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naive cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the rol…
CD32 ligation promotes the activation of CD4+T cells
2018
Low affinity receptors for the Fc portion of IgG (FcγRs) represent a critical link between innate and adaptive immunity. Immune complexes (ICs) are the natural ligands for low affinity FcγRs, and high levels of ICs are usually detected in both, chronic viral infections and autoimmune diseases. The expression and function of FcγRs in myeloid cells, NK cells and B cells have been well characterized. By contrast, there are controversial reports about the expression and function of FcγRs in T cells. Here, we demonstrated that ∼2% of resting CD4+ T cells express cell surface FcγRII (CD32). Analysis of CD32 expression in permeabilized cells revealed an increased proportion of CD4+CD32+ T cells (∼…
Bordeaux 2018: Wine, Cheese, and γδ T Cells
2019
The first ‘International γδ T cell conference’ took place in Denver, CO (USA) in 2004. Since then, a new meeting is held every two years. During each conference, all participants voted to choose between candidate bids for where to hold the next conference. At the conference held in London in 2016, a majority opted for the bid from a team proposing the 2018 event be held in Bordeaux, France – which is where we therefore gathered on 7-10th of June 2018. The meeting was an undisputed success and it gave us the opportunity to take stock of the increasing basic knowledge about γδ T cells as well as the rapidly expanding interest and activities developing using γδ T cells towards clinical applica…
CD38-Specific Biparatopic Heavy Chain Antibodies Display Potent Complement-Dependent Cytotoxicity Against Multiple Myeloma Cells
2018
CD38 is overexpressed by multiple myeloma cells and has emerged as a target for therapeutic antibodies. Nanobodies are soluble single domain antibody fragments derived from the VHH variable domain of heavy chain antibodies naturally occurring in camelids. We previously identified distinct llama nanobodies that recognize three non-overlapping epitopes of the extracellular domain of CD38. Here, we fused these VHH domains to the hinge, CH2, and CH3 domains of human IgG1, yielding highly soluble chimeric llama/human heavy chain antibodies (hcAbs). We analyzed the capacity of these hcAbs to mediate complement-dependent cytotoxicity (CDC) to CD38-expressing human multiple myeloma and Burkitt lymp…
Interleukin-22 in Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation
2016
International audience; Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for hematologic malignancies and non-malignant diseases. Because of the lower toxicity of reduced intensity conditioning, the number of transplants is in constant increase. However, allo-HSCT is still limited by complications, such as graft-versus-host disease (GVHD), which is associated with important morbidity and mortality. Acute GVHD is an exacerbated inflammatory response that leads to the destruction of healthy host tissues by donor immune cells. Recently, the contribution of innate immunity in GVHD triggering has been investigated by several groups and resulted in …
A non-functional neoepitope specific CD8+ T-cell response induced by tumor derived antigen exposure in vivo
2018
Cancer-associated mutations, mostly single nucleotide variations, can act as neoepitopes and prime targets for effective anti-cancer T-cell immunity. T cells recognizing cancer mutations are critical for the clinical activity of immune checkpoint blockade (ICB) and they are potent vaccine antigens. High frequencies of mutation-specific T cells are rarely spontaneously induced. Hence, therapies that broaden the tumor specific T-cell response are of interest. Here, we analyzed neoepitope-specific CD8+ T-cell responses mounted either spontaneously or after immunotherapy regimens, which induce local tumor inflammation and cell death, in mice bearing tumors of the widely used colon carcinoma cel…
Elevated sodium leads to the increased expression of HSP60 and induces apoptosis in HUVECs
2017
Atherosclerosis is the leading cause of death in the world. We have previously shown that expression of heat shock protein 60 (HSP60) on the surface of endothelial cells is the main cause of initiating the disease as it acts as a T cell auto-antigen and can be triggered by classical atherosclerosis risk factors, such as infection (e.g. Chlamydia pneumoniae), chemical stress (smoking, oxygen radicals, drugs), physical insult (heat, shear blood flow) and inflammation (inflammatory cytokines, lipopolysaccharide, oxidized low density lipoprotein, advanced glycation end products). In the present study, we show that increasing levels of sodium chloride can also induce an increase in intracellular…