Myoinjury transiently activates muscle antigen-specific CD8+ T cells in lymph nodes in a mouse model.: Myoinjury and CD8+ T-cell activation

International audienceOBJECTIVE: To investigate the influence of myoinjury on antigen presentation to T cells in draining lymph nodes (LNs). METHODS: Muscle crush was performed in mice injected with exogenous ovalbumin (OVA) and in transgenic SM-OVA mice expressing OVA as a muscle-specific self antigen. Antigen exposure and the resulting stimulation of T cell proliferation in draining LNs was assessed by transferring carboxyfluorescein succinimidyl ester (CFSE)-labeled OVA-specific CD8+ and CD4+ T cells from OT-I and OT-II mice and by measuring the dilution of CFSE, which directly reflects their proliferation. The role of monocyte-derived dendritic cells (DCs) in T cell priming was assessed using pharmacologic blockade of DC migration. Immunofluorescence was used to detect CD8+ T cells, inflammatory monocyte-derived DCs, and type I major histocompatibility complex (MHC)-expressing myofibers in crushed muscle, and to assess expression of perforin, interferon-γ (IFNγ), interleukin-2 (IL-2), IL-10, and transforming growth factor β1 (TGFβ1). RESULTS: OVA injection into intact muscle induced strong proliferation of CD4+ and CD8+ T cells, indicating efficient exposure of soluble antigens in draining LNs. OVA-specific CD8+ T cell proliferation in draining LNs of SM-OVA mice required myoinjury and was unaffected by pharmacologic inhibition of monocyte-derived DC migration. On day 7 postinjury, activated CD8+ T cells expressing perforin, IFNγ and IL-2 were transiently detected in crushed muscle, and these cells were in close contact with class I MHC-positive regenerating myofibers. Beginning on day 7, the immunosuppressive cytokines IL-10 and TGFβ1 were conspicuously expressed by CD11b+ cells, and CD8+ T cells rapidly disappeared from the healing muscle. CONCLUSION: Myofiber damage induces an episode of muscle antigen-specific CD8+ T cell proliferation in draining LNs. Activated CD8+ T cells transiently infiltrate the injured muscle, with prompt control by immunosuppressive cues. Inadequate control might favor sustained autoimmune myositis

The IgG2 isotype of anti-transcription intermediary factor 1-gamma autoantibodies is a biomarker of mortality and cancer in adult dermatomyositis

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Brain proteomic modifications associated to protective effect of grape extract in a murine model of obesity

International audiencen recent years, the obesity epidemic has developed into a major health crisis worldwide. With current treatments limited to expensive, high-risk surgery and minimally efficacious pharmacotherapy, new therapeutic options are urgently needed to fight against this alarming trend. Though brain dysfunction has been studied linked to high fat diet (HFD) and grape seed and skin extract (GSSE) correction, the proteomic modifications linking the two effects on brain lipotoxicity are not well understood. To this end rats were exposed for 8 weeks to HFD treatment, to GSSE (500 mg/kg BW) and to binary mixture of HFD and GSSE to gain insight into the potential pathways altered with metabolic disease and the protection afforded by GSSE. Significant modifications of brain proteins were detected using mass spectrometry-based differential proteomics. These proteins were mainly related to oxidative stress, glycolysis and calcium signaling. Additionally, proteins involved in the cytoskeleton were also affected by HFD treatment. Interestingly, whether up- or down regulated protein abundances, GSSE corrected most of the disturbances of HFD treatment. These findings provide impetus for future therapeutic investigation on GSSE against other metabolic disorders

Restoration of Anal Sphincter Function after Myoblast Cell Therapy in Incontinent Rats

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Temporal dynamics of demersal chondrichthyan species in the central western Mediterranean Sea: The case study in Sardinia Island

Occurrence, abundance and size trends of 25 demersal Chondrichthyes (10 Sharks: 3 Carcharhiniformes, 2 Hexanchiformes, 5 Squaliformes; 14 Batoids: 3 Myliobatiformes, 8 Rajiformes, 3 Torpediniformes and 1 Holocephalan: 1 Chimaeriformes) collected from 22 years (1994–2015) of Mediterranean International Trawl Surveys (MEDITS) around Sardinian seas, were given. Data relative to two strata, the continental shelf (10–200 m), the slope (201–800 m), and the overall (10–800 m), were analyzed in order to identify the general species distribution of their habitat preference. From the gathered data it appeared that the shelf was mostly inhabited by batoids while the slope by sharks. Only the small-spotted catshark Scyliorhinus canicula and the thornback skate Raja clavata were equally distributed with high values of occurrence and abundance both in the shelf and in the slope. All the other species showed a preferential distribution only in one stratum (shelf or slope). In general, temporal trends of abundance indexes were stable or increasing in all strata. GAM analysis also confirmed a stable trend. Almost all species displayed stable in size structure analysis, apart from R. brachyura and Dipturus oxyrinchus that showed a statistically increasing trend. Although the investigated chondrichthyan species seemed to display a not alarming status of conservation in Sardinian seas, more investigation should be done to assure a proper management of this threatened resource

Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling pathway and exhibits a dual function

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IgG N-Glycosylation from Patients with Pemphigus Treated with Rituximab

International audiencePemphigus is a life-threatening auto-immune blistering disease of the skin and mucous membrane that is caused by the production of auto-antibodies (auto-Abs) directed against adhesion proteins: desmoglein 1 and 3. We demonstrated in the "Ritux3" trial, the high efficacy of rituximab, an anti-CD20 recombinant monoclonal antibody, as the first-line treatment for pemphigus. However, 25% of patients relapsed during the six-month period after rituximab treatment. These early relapses were associated with a lower decrease in anti-desmoglein auto-Abs after the initial cycle of rituximab. The N-glycosylation of immunoglobulin-G (IgG) can affect their affinity for Fc receptors and their serum half-life. We hypothesized that the extended half-life of Abs could be related to modifications of IgG N-glycans. The IgG N-glycome from pemphigus patients and its evolution under rituximab treatment were analyzed. Pemphigus patients presented a different IgG N-glycome than healthy donors, with less galactosylated, sialylated N-glycans, as well as a lower level of N-glycans bearing an additional N-acetylglucosamine. IgG N-glycome from patients who achieved clinical remission was not different to the one observed at baseline. Moreover, our study did not identify the N-glycans profile as discriminating between relapsing and non-relapsing patients. We report that pemphigus patients present a specific IgG N-glycome. The changes observed in these patients could be a biomarker of autoimmunity susceptibility rather than a sign of inflammation

Additional file 6: of Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors

TNF receptor (TNFR)1 and TNFR2 have no effect on RasGRP1 and RasGRP3 gene expression level in T and B cells respectively. Quantitative PCR analysis was performed to measure RasGRP1 and RasGRP3 gene expression levels in T and B cells respectively from three healthy controls. T or B cells were exposed to anti-TNFR1 or anti-TNFR2 neutralizing antibodies without TNFα for 48 hours. The relative expression levels (in arbitrary units (AU)) of RasGRP1 and RasGRP3 were normalized with 18S RNA abundance. Mean ± standard error of the mean were compared using one-way analysis of variance followed by Bonferroni post-hoc test. (TIF 47 kb