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Scooped by
Gilbert C FAURE
December 10, 2018 3:45 AM
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Immunosenescence is characterized by deterioration of the immune system caused by aging which induces changes to innate and adaptive immunity. Immunosenescence affects function and phenotype of immune cells, such as expression and function of receptor
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Scooped by
Gilbert C FAURE
December 8, 2018 4:06 AM
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Author summary Soluble pattern recognition molecules, PRMs, are components of the humoral arm of innate immunity. The long pentraxin 3, PTX3, is a prototypic soluble PRM that is produced in response to primary inflammatory signals.
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Scooped by
Gilbert C FAURE
December 7, 2018 11:47 AM
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This Review discusses the importance of autophagy in controlling immune cell differentiation and homeostasis. The authors consider the diverse mechanisms through which autophagy functions to shape the immune system, highlighting its role in the dynamic regulation of metabolism.
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Scooped by
Gilbert C FAURE
December 6, 2018 2:42 PM
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Leukocytes continuously circulate throughout the body. He et al. demonstrate that
trafficking patterns of major leukocyte subsets occur in a rhythmic manner dependent
on the time-of-day-dependent expression of lineage- and tissue-specific factors. This
influences the inflammatory response and leukemic tumor burden and translates to the
migration behavior of human primary lymphocytes.
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Scooped by
Gilbert C FAURE
December 6, 2018 12:20 PM
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Germinal center (GC) B cells are essential to generating protective antibody responses and are selected through a process of affinity maturation. Kwak et al . now define intrinsic properties of human GC B cells that are critical to antigen affinity discrimination. They identified BCR-containing actin-rich pod-like structures that facilitated formation of highly stable synapses and antigen internalization but only when GC B cells engaged high-affinity antigens. These findings reveal the importance of these structures in setting thresholds for affinity selection and driving GC B cell responses.
Protective antibody responses to vaccination or infection depend on affinity maturation, a process by which high-affinity germinal center (GC) B cells are selected on the basis of their ability to bind, gather, and present antigen to T follicular helper (Tfh) cells. Here, we show that human GC B cells have intrinsically higher-affinity thresholds for both B cell antigen receptor (BCR) signaling and antigen gathering as compared with naïve B cells and that these functions are mediated by distinct cellular structures and pathways that ultimately lead to antigen affinity– and Tfh cell–dependent differentiation to plasma cells. GC B cells bound antigen through highly dynamic, actin- and ezrin-rich pod-like structures that concentrated BCRs. The behavior of these structures was dictated by the intrinsic antigen affinity thresholds of GC B cells. Low-affinity antigens triggered continuous engagement and disengagement of membrane-associated antigens, whereas high-affinity antigens induced stable synapse formation. The pod-like structures also mediated affinity-dependent antigen internalization by unconventional pathways distinct from those of naïve B cells. Thus, intrinsic properties of human GC B cells set thresholds for affinity selection.
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Suggested by
LIGHTING
December 6, 2018 6:49 AM
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Golden star tunicate could help scientists uncover new approaches for preventing organ rejection, treating cancer
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Scooped by
Gilbert C FAURE
December 5, 2018 9:03 AM
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Intratumoral T cells that are capable of recognizing adjacent tumor tissue antigens can be exceedingly rare.
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Scooped by
Gilbert C FAURE
December 5, 2018 9:00 AM
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With a new crew arriving at the International Space Station, astronauts will be relieved to know that they won't have to worry about a major aspect of their immune system being compromised. While researchers know a lot about ...
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Scooped by
Gilbert C FAURE
December 3, 2018 12:06 PM
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Influenza A viruses cause pandemics when they cross between species. In this Review, Barclay and colleagues examine the host barriers that influenza A viruses must overcome to initiate a pandemic in humans and describe how, on crossing the species barrier, the virus mutates to establish new interactions with the human host.
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Scooped by
Gilbert C FAURE
November 29, 2018 12:14 PM
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UT Southwestern biochemist and Breakthrough Prize winner Dr. Zhijian "James" Chen's newest study answers a long-standing question in the field of innate immunity.
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Scooped by
Gilbert C FAURE
November 29, 2018 4:32 AM
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Lawson et al. review recent advances in single-cell technologies and discuss in detail how they can be leveraged to understand tumour heterogeneity and metastasis.
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Scooped by
Gilbert C FAURE
November 27, 2018 8:26 AM
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Scooped by
Gilbert C FAURE
November 23, 2018 1:25 PM
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![Figure][1]
γδ T cells are highly conserved in jawed vertebrates, suggesting an essential role in the immune system. However, γδ T cell–deficient Tcrd −/− mice display surprisingly mild phenotypes. We hypothesized that the lack of γδ T cells in constitutive Tcrd −/− mice is functionally compensated by other lymphocytes taking over genuine γδ T cell functions. To test this, we generated a knock-in model for diphtheria toxin–mediated conditional γδ T cell depletion. In contrast to IFN-γ–producing γδ T cells, IL-17–producing γδ T cells (Tγδ17 cells) recovered inefficiently after depletion, and their niches were filled by expanding Th17 cells and ILC3s. Complementary genetic fate mapping further demonstrated that Tγδ17 cells are long-lived and persisting lymphocytes. Investigating the function of γδ T cells, conditional depletion but not constitutive deficiency protected from imiquimod-induced psoriasis. Together, we clarify that fetal thymus-derived Tγδ17 cells are nonredundant local effector cells in IL-17–driven skin pathology.
[1]: pending:yes
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Scooped by
Gilbert C FAURE
December 8, 2018 7:21 AM
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Pain. 2018 Nov 29. doi: 10.1097/j.pain.0000000000001449.[Epub ahead of print]...
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Scooped by
Gilbert C FAURE
December 7, 2018 2:37 PM
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In this issue of JEM , the study by Chen et al. (<https://doi.org/10.1084/jem.20181031>) reveals a previously unrecognized role of cellular nucleic acid–binding protein (Cnbp) as a novel transcriptional regulator of interleukin-12β (IL-12β) transcription and IL-12–driven, Th1-mediated immune responses, which has important implications for both host defense and inflammatory disease.
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Scooped by
Gilbert C FAURE
December 7, 2018 4:32 AM
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Disruption of the circadian clock has been linked to cancer and alterations in cancer metabolism and this has implications for therapeutic development.
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Scooped by
Gilbert C FAURE
December 6, 2018 12:22 PM
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Mucosal-associated invariant T (MAIT) cells are abundant T cells with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed the first transcriptomic analysis of murine MAIT cells. MAIT1 (RORγtneg) and MAIT17 (RORγt+) subsets were markedly distinct from mainstream T cells, but quasi-identical to NKT1 and NKT17 subsets. The expression of similar programs was further supported by strong correlations of MAIT and NKT frequencies in various organs. In both mice and humans, MAIT subsets expressed gene signatures associated with tissue residency. Accordingly, parabiosis experiments demonstrated that MAIT and NKT cells are resident in the spleen, liver, and lungs, with LFA1/ICAM1 interactions controlling MAIT1 and NKT1 retention in spleen and liver. The transcriptional program associated with tissue residency was already expressed in thymus, as confirmed by adoptive transfer experiments. Altogether, shared thymic differentiation processes generate “preset” NKT and MAIT subsets with defined effector functions, associated with specific positioning into tissues.
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Scooped by
Gilbert C FAURE
December 6, 2018 12:08 PM
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The pathophysiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis is not yet completely understood but innate immunity is a major factor. In this Review, the evidence for macrophage involvement in the development of liver steatosis, inflammation and fibrosis is discussed.
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Suggested by
LIGHTING
December 5, 2018 12:54 PM
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Adequate perception of immunologically important pathogen-associated molecular patterns like lipopolysaccharide and bacterial lipoproteins is essential for efficient innate and adaptive immune responses. In the context of Gram-negative infection, bactericidal/permeability-increasing protein (BPI) neutralizes endotoxic activity of lipopolysaccharides, and thus prohibits hyperactivation. So far, no immunological function of BPI has been described in Gram-positive infections. Here we show a significant elevation of BPI in Gram-positive meningitis and surprisingly a positive correlation between BPI and pro-inflammatory markers like TNF. To clarify the underlying mechanisms, we identify BPI ligands of Gram-positive origin, specifically bacterial lipopeptides and lipoteichoic acids, and determine essential structural motifs for this interaction. Importantly, the interaction of BPI with these newly defined ligands significantly enhances the immune response in peripheral blood mononuclear cells mediated by Gram-positive bacteria, and thereby ensures their sensitive perception. In conclusion, we define BPI as an immune enhancing pattern recognition molecule in Gram-positive infections.
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Scooped by
Gilbert C FAURE
December 5, 2018 9:02 AM
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Blocking the function of the NKG2A inhibitory receptor, as well as its ligand, promotes
robust anti-tumor immunity in a number of animal tumor models, including one refractory
to PD-1 blockade.
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Suggested by
LIGHTING
December 4, 2018 3:42 PM
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Scooped by
Gilbert C FAURE
December 3, 2018 11:45 AM
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We have previously reported that a group of host cellular microRNAs (miRNAs; miR-34a-5p, miR-122-5p, miR-145-5p, miR-146a-5p, miR-210-3p) are released into the blood during sepsis, some of which are capable of inducing complement activation, cytokine production, and leukocyte migration.
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Suggested by
LIGHTING
November 29, 2018 5:04 AM
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Recent studies have established γδ T cells as critical players in a broad range of infections, antitumor surveillance, autoimmune diseases and tissue homeostasis. However, differentiation of γδ T cells in the adult thymus remains poorly understood, due to the rare frequency of this lineage. Here, we infer high-resolution developmental trajectories of this rare population by single-cell RNA-sequencing. We reveal previously unknown subtypes and identify the transcription factor c-MAF as a novel key regulator of IL-17-producing γδ T cell (γδT17) differentiation. c-MAF knockout mice exhibit a complete block in γδT17 differentiation, absence of these cells from peripheral organs, and protection from an autoimmune phenotype in a psoriasis model. Single-cell RNA-sequencing of Sox13 and Rorc knockout mice pinpoints c-MAF as an essential missing link between these lineage-specifying factors. These findings significantly enhance our understanding of γδ T cell ontogeny. Our experimental strategy provides a blueprint for deciphering differentiation of rare cell types.
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Scooped by
Gilbert C FAURE
November 27, 2018 1:34 PM
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Coencapsulation of T cells and target cells into arrays of subnanoliter droplets improves the identification of functional T cell receptors. Although this is an elegant demonstration of the utility of droplet microfluidics, some limitations of this proof-of-concept study need to be addressed. It has yet to be shown that this technology works with patient-derived target cells and T cells, which contain far more clonotypes than demonstrated with the two TCR reporter cell lines used here. Furthermore, the use of transduced GFP expression as a readout for T cell activation is slow and likely impractical when working with patient-derived cells. Nonetheless, the accurate identification of high activity TCRs by high-throughput T cell screening in automatable workflows could lead to faster and more effective patient-specific immunotherapies. It appears that finding compatible binding partners in the lab, as with love, may simply be a numbers game.
Via Krishan Maggon
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