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Foxp3 + T regulatory (Treg) cells prevent inflammatory disease but the mechanistic basis of suppression is not understood completely. Gene silencing by RNA interference can act in a cell-autonomous and non-cell-autonomous manner, providing mechanisms of intercellular regulation. Here, we demonstrate that non-cell-autonomous gene silencing, mediated by miRNA-containing exosomes, is a mechanism...
T regulatory (Treg) cells enforce peripheral tolerance through regulation of diverse immune responses in a context-dependent manner. Okoye et al. show one way in which Treg cells suppress Th1 cell responses is through nonautonomous gene silencing mediated by microRNA-containing exosomes.
Maintenance of immunological memory has been proposed to rely on stem-cell-like lymphocytes. However, data supporting this hypothesis are focused on the developmental potential of lymphocyte populations and are thus insufficient to establish the functional hallmarks of stemness. Here, we investigated self-renewal capacity and multipotency of individual memory lymphocytes by in vivo fate mapping of...
In this issue of Immunity, Graef et al. (2014) demonstrate self-renewal and multipotency of a single CD62L + memory T cell across serial adoptive transfers and infection-driven re-expansions, providing evidence of true stemness within the T cell memory compartment.
How diversity of the microbiota is generated and maintained is an open question. In this issue of Immunity, Kawamoto et al. show that T follicular regulatory cells foster microbiota diversity via the regulation of IgA selection.
Polarization of effector CD4 + T cells can be influenced by both antigen-specific signals and by pathogen- or adjuvant-induced cytokines, with current models attributing a dominant role to the latter. Here we have examined the relationship between these factors in shaping cell-mediated immunity by using intravital imaging of CD4 + T cell interactions with dendritic cells (DCs) exposed...
Macrophage and dendritic cell (DC) progenitors (MDPs) produce macrophages and DCs but not other hematopoietic lineages. In this issue of Immunity, Sathe et al. (2014) show that isolated MDP populations hardly contain such bipotent progenitors at clonal levels, arguing against the existence of MDPs.
The relationship between dendritic cells (DCs) and macrophages is often debated. Here we ask whether steady-state, lymphoid-tissue-resident conventional DCs (cDCs), plasmacytoid DCs (pDCs), and macrophages share a common macrophage-DC-restricted precursor (MDP). Using new clonal culture assays combined with adoptive transfer, we found that MDP fractions isolated by previous strategies are dominated...
Macrophages are distributed in tissues throughout the body and contribute to both homeostasis and disease. Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes. Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are...
Chronic, low-grade adipose tissue inflammation is a key etiological mechanism linking the increasing incidence of type 2 diabetes (T2D) and obesity. It is well recognized that the immune system and metabolism are highly integrated, and macrophages, in particular, have been identified as critical effector cells in the initiation of inflammation and insulin resistance. Recent advances have been made...
Generation of CD8 + memory T cells requires metabolic reprogramming that is characterized by enhanced mitochondrial fatty-acid oxidation (FAO). However, where the fatty acids (FA) that fuel this process come from remains unclear. While CD8 + memory T cells engage FAO to a greater extent, we found that they acquired substantially fewer long-chain FA from their external environment than...
The tumor microenvironment is a complex ecology of cells that evolves with and provides support to tumor cells during the transition to malignancy. Among the innate and adaptive immune cells recruited to the tumor site, macrophages are particularly abundant and are present at all stages of tumor progression. Clinical studies and experimental mouse models indicate that these macrophages generally play...
Foxp3 + T cells play a critical role for the maintenance of immune tolerance. Here we show that in mice, Foxp3 + T cells contributed to diversification of gut microbiota, particularly of species belonging to Firmicutes. The control of indigenous bacteria by Foxp3 + T cells involved regulatory functions both outside and inside germinal centers (GCs), consisting of suppression...
Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two...
We host a world inside, and every day, new evidence reveals how relevant our microbiota is for daily living. In the most recent issue of Cell, Muller and colleagues demonstrate that microbiota commensals also influence colon peristalsis via a direct effect of muscolaris externae macrophages (Muller et al., 2014).
Memory T cells display a distinct metabolic profile compared to effector T cells. In this issue of Immunity, O’Sullivan et al. (2014) report that memory T cells activate a “futile cycle” of de novo fatty-acid synthesis and concurrent fatty-acid oxidation to generate ATP for cell survival.
Memory CD8 + T cells are programmed during the primary response for robust secondary responsiveness. Here we show that CD8 + T cells responding to different epitopes of influenza virus received qualitatively different signals during the primary response that altered their secondary responsiveness. Nucleoprotein (NP)-specific CD8 + T cells encountered antigen on CD40-licensed,...
Immunoglobulin E (IgE) antibodies are known for triggering immediate hypersensitivity reactions such as food anaphylaxis. In this study, we tested whether they might additionally function to amplify nascent antibody and T helper 2 (Th2) cell-mediated responses to ingested proteins and whether blocking IgE would modify sensitization. By using mice harboring a disinhibited form of the IL-4 receptor,...
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