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Objective: Myasthenia gravis (MG) is a neuromuscular disease mediated by antibodies against the acetylcholine receptor (AChR). The thymus plays a primary role in AChR-MG and is characterized by a type I interferon (IFN) signature linked to IFN-β. We investigated if AChR-MG was characterized by an IFN-I signature in the blood, and further investigated the chronic thymic IFN-I signature., Methods: Serum levels of IFN-β and IFN-α subtypes, and mRNA expression for IFN-I subtypes and IFN-stimulated genes in peripheral mononuclear blood cells (PBMCs) were analyzed. The contribution of endogenous nucleic acids in thymic expression of IFN-I subtypes was investigated in human thymic epithelial cell cultures and the mouse thymus. By immunohistochemistry, thymic CD68 + and CD163 + macrophages were analyzed in AChR-MG. To investigate the impact of a decrease in thymic macrophages, mice were treated with an anti-CSF1R antibody., Results: No IFN-I signature was observed in the periphery emphasizing that the IFN-I signature is restricted to the MG thymus. Molecules mimicking endogenous dsDNA signalization (Poly(dA:dT) and 2'3'-cGAMP), or dexamethasone-induced necrotic thymocytes increased IFN-β and α-AChR expression by thymic epithelial cells, and in the mouse thymus. A significant decrease in thymic macrophages was demonstrated in AChR-MG. In mice, a decrease in thymic macrophages led to an increase of necrotic thymocytes associated with IFN-β and α-AChR expression., Interpretation: These results suggest that the decrease of thymic macrophages in AChR-MG impairs the elimination of apoptotic thymocytes favoring the release of endogenous nucleic acids from necrotic thymocytes. In this inflammatory context, thymic epithelial cells may overexpress IFN-β, which specifically induces α-AChR, resulting in self-sensitization and thymic changes leading to AChR-MG. ANN NEUROL 2023;93:643-654., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Myasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR + MG, we performed an in-depth analysis of peripheral mononuclear blood cells (PBMCs) using mass cytometry. PBMCs from 24 AChR + MG patients without thymoma and 16 controls were stained with a panel of 37 antibodies. Using both unsupervised and supervised approaches, we observed a decrease in monocytes, for all subpopulations: classical, intermediate, and non-classical monocytes. In contrast, an increase in innate lymphoid cells 2 (ILC2s) and CD27 - γδ T cells was observed. We further investigated the dysregulations affecting monocytes and γδ T cells in MG. We analyzed CD27 - γδ T cells in PBMCs and thymic cells from AChR + MG patients. We detected the increase in CD27 - γδ T cells in thymic cells of MG patients suggesting that the inflammatory thymic environment might affect γδ T cell differentiation. To better understand changes that might affect monocytes, we analyzed RNA sequencing data from CD14 + PBMCs and showed a global decrease activity of monocytes in MG patients. Next, by flow cytometry, we especially confirmed the decrease affecting non-classical monocytes. In MG, as for other B-cell mediated autoimmune diseases, dysregulations are well known for adaptive immune cells, such as B and T cells. Here, using single-cell mass cytometry, we unraveled unexpected dysregulations for innate immune cells. If these cells are known to be crucial for host defense, our results demonstrated that they could also be involved in autoimmunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Verdier, Fayet, Hemery, Truffault, Pinzón, Demeret, Behin, Fadel, Guihaire, Corneau, Blanc, Berrih-Aknin and Le Panse.)

NK cells orchestrate the tumor destruction and control metastasis in a coordinated way with other immune cells of the tumor microenvironment. However, NK cell infiltration in the tumor microenvironment is limited, and tumor cells have developed numerous mechanisms to escape NK cell attack. As a result, NK cells that have been able to infiltrate the tumors are exhausted, and metabolically and functionally impaired. Depending this impairment the prognostic and theranostic values of NK cells differ depending on the studies, the type of cancer, the stage of tumor and the nature of the tumor microenvironment. Extensive studies have been done to investigate different strategies to improve the NK cell function, and nowadays, a battery of therapeutic tools are being tested, with promising results., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The mammalian auditory system extracts features from the acoustic environment based on the responses of spatially distributed sets of neurons in the subcortical and cortical auditory structures. The characteristic responses of these neurons (linearly approximated by their spectro-temporal receptive fields, or STRFs) suggest that auditory representations are formed, as early as in the inferior colliculi, on the basis of a time, frequency, rate (temporal modulations) and scale (spectral modulations) analysis of sound. However, how these four dimensions are integrated and processed in subsequent neural networks remains unclear. In this work, we present a new methodology to generate computational insights into the functional organization of such processes. We first propose a systematic framework to explore more than a hundred different computational strategies proposed in the literature to process the output of a generic STRF model. We then evaluate these strategies on their ability to compute perceptual distances between pairs of environmental sounds. Finally, we conduct a meta-analysis of the dataset of all these algorithms' accuracies to examine whether certain combinations of dimensions and certain ways to treat such dimensions are, on the whole, more computationally effective than others. We present an application of this methodology to a dataset of ten environmental sound categories, in which the analysis reveals that (1) models are most effective when they organize STRF data into frequency groupings-which is consistent with the known tonotopic organization of receptive fields in auditory structures -, and that (2) models that treat STRF data as time series are no more effective than models that rely only on summary statistics along time-which corroborates recent experimental evidence on texture discrimination by summary statistics.

The purpose of the present study was to examine the activity of the human Lactobacillus acidophilus strain LB, which secretes an antibacterial substance(s) against Helicobacter pylori in vitro and in vivo. The spent culture supernatant (SCS) of the strain LB (LB-SCS) dramatically decreased the viability of H. pylori in vitro independent of pH and lactic acid levels. Adhesion of H. pylori to the cultured human mucosecreting HT29-MTX cells decreased in parallel with the viability of H. pylori. In conventional mice, oral treatment with the LB-SCS protected against infection with Helicobacter felis. Indeed, at both 8 and 49 days post-LB-SCS treatment (29 and 70 days postinfection), inhibition of stomach colonization by H. felis was observed, and no evidence of gastric histopathological lesions was found. LB-SCS treatment inhibits the H. pylori urease activity in vitro and in H. pylori that remained associated with the cultured human mucosecreting HT29-MTX cells. Moreover, a decrease in urease activity was detected in the stomach of the mice infected with H. felis and treated with LB-SCS.