Search results for "57"
showing 10 items of 4186 documents
Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity
2016
Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4+Foxp3- T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self-antigen, while Tconv cell development was not negatively affected. Thymus-derived Treg cells were selected by self-antigens in a specific manner, while autoreactive Tconv cells were produced through degenerate recognition of distinct antigens. These distinct modes of development were associated with the expressi…
Mast cells crosstalk with B cells in the gut and sustain IgA response in the inflamed intestine.
2021
B lymphocytes are among the cell types whose effector functions are modulated by mast cells (MCs). The B/MC crosstalk emerged in several pathological settings, notably the colon of inflammatory bowel disease (IBD) patients is a privileged site in which MCs and IgA+ cells physically interact. Herein, by inducing conditional depletion of MCs in red MC and basophil (RMB) mice, we show that MCs control B cell distribution in the gut and IgA serum levels. Moreover, in dextran sulfate sodium (DSS)-treated RMB mice, the presence of MCs is fundamental for the enlargement of the IgA+ population in the bowel and the increase of systemic IgA production. Since both conventional B-2 and peritoneal-deriv…
Signalling strength determines proapoptotic functions of STING
2017
Mammalian cells use cytosolic nucleic acid receptors to detect pathogens and other stress signals. In innate immune cells the presence of cytosolic DNA is sensed by the cGAS–STING signalling pathway, which initiates a gene expression programme linked to cellular activation and cytokine production. Whether the outcome of the STING response varies between distinct cell types remains largely unknown. Here we show that T cells exhibit an intensified STING response, which leads to the expression of a distinct set of genes and results in the induction of apoptosis. Of note, this proapoptotic STING response is still functional in cancerous T cells and delivery of small molecule STING agonists prev…
Collective Infection of Cells by Viral Aggregates Promotes Early Viral Proliferation and Reveals a Cellular-Level Allee Effect
2018
In addition to the conventional release of free, individual virions, virus dispersal can involve multi-virion assemblies that collectively infect cells. However, the implications of collective infection for viral fitness remain largely unexplored. Using vesicular stomatitis virus, here, we compare the fitness of free versus saliva-aggregated viral particles. We find that aggregation has a positive effect on early progeny production, conferring a fitness advantage relative to equal numbers of free particles in most cell types. The advantage of aggregation resides, at least partially, in increasing the cellular multiplicity of infection. In mouse embryonic fibroblasts, the per capita, short-t…
Tnfaip3 expression in pulmonary conventional type 1 Langerin‐expressing dendritic cells regulates T helper 2‐mediated airway inflammation in mice
2020
Abstract Background Conventional type 1 dendritic cells (cDC1s) control anti‐viral and anti‐tumor immunity by inducing antigen‐specific cytotoxic CD8+ T‐cell responses. Controversy exists whether cDC1s also control CD4+ T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcription factor NF‐κB, might determine the precise outcome of Th‐cell differentiation upon encounter with cDC1s. To investigate the role of activated cDC1s in Th2‐driven immune responses, pulmonary cDC1s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF‐κB signaling. Methods To target pulmonary cDC1s, Cd207 (Lan…
MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes.
2015
Oligodendrocytes are the myelinating glial cells of the central nervous system (CNS). Myelin is formed by extensive wrapping of oligodendroglial processes around axonal segments which ultimately allows a rapid saltatory conduction of action potentials within the CNS and sustains neuronal health. The non-receptor tyrosine kinase Fyn is an important signaling molecule in oligodendrocytes. It controls the morphological differentiation of oligodendrocytes and is an integrator of axon-glial signaling cascades leading to localized synthesis of Myelin Basic Protein (MBP) which is essential for myelin formation. The abundant Myelin-Associated Oligodendrocytic Basic Protein (MOBP) resembles MBP in s…
Bifunctional Hydrogels Containing the Laminin Motif IKVAV Promote Neurogenesis
2017
Summary Engineering of biomaterials with specific biological properties has gained momentum as a means to control stem cell behavior. Here, we address the effect of bifunctionalized hydrogels comprising polylysine (PL) and a 19-mer peptide containing the laminin motif IKVAV (IKVAV) on embryonic and adult neuronal progenitor cells under different stiffness regimes. Neuronal differentiation of embryonic and adult neural progenitors was accelerated by adjusting the gel stiffness to 2 kPa and 20 kPa, respectively. While gels containing IKVAV or PL alone failed to support long-term cell adhesion, in bifunctional gels, IKVAV synergized with PL to promote differentiation and formation of focal adh…
Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses
2016
Targeting antigen combined with adjuvants to hepatic antigen-presenting cells (APCs) is essential for the induction of intrahepatic T cellular immunity controlling and resolving viral infections of the liver. Intravenous injection of antigen-loaded nanoparticles is a promising approach for the delivery of antigens to liver APCs. Accordingly, polymeric nanocapsules (NCs) synthesized exclusively of hepatitis C virus non-structural protein 5A (NS5A) and the adjuvant monophosphoryl lipid A (MPLA) adsorbed to the nanocapsule surface were developed. Aim of the present study was the evaluation of the in vitro and in vivo behavior of MPLA-functionalized NS5A-NCs regarding the interaction with liver…
Neurofibromatosis type 2 tumor suppressor protein is expressed in oligodendrocytes and regulates cell proliferation and process formation.
2017
The neurofibromatosis type 2 (NF2) tumor suppressor protein Merlin functions as a negative regulator of cell growth and actin dynamics in different cell types amongst which Schwann cells have been extensively studied. In contrast, the presence and the role of Merlin in oligodendrocytes, the myelin forming cells within the CNS, have not been elucidated. In this work, we demonstrate that Merlin immunoreactivity was broadly distributed in the white matter throughout the central nervous system. Following Merlin expression during development in the cerebellum, Merlin could be detected in the cerebellar white matter tract at early postnatal stages as shown by its co-localization with Olig2-positi…
IL-17 controls central nervous system autoimmunity through the intestinal microbiome
2021
Interleukin-17A- (IL-17A) and IL-17F-producing CD4(+) T helper cells (T(H)17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). T-H 17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, T-H 17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which…