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Suggested by
LIGHTING
January 19, 2017 8:03 AM
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The January issue of the BSI’s official journal Clinical & Experimental Immunology is a special issue on immunosenescence, containing a fascinating set of review articles summarising our current knowledge in this area and what we still need to find out. Here, BSI member Dr Natalie Riddell, Lecturer in Immunology, University of Surrey, discusses the key papers highlighted in this issue.
Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is required. Immunity is influenced by a complex set of tumour, host and environmental factors that govern the strength and timing of the anticancer response. Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy. In the context of the cancer-immunity cycle, such factors combine to represent the inherent immunological status — or 'cancer–immune set point' — of an individual.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
January 18, 2017 6:28 AM
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The Mononuclear Phagocyte System (MPS) of vertebrates is composed of monocytes, macrophages and dendritic cells. Together, they form part of the first line of immune defense against a variety of pathogens (bacteria, fungi, parasites and viruses), and thus play an important role in maintaining organism homeostasis. The mode of transmission, type of replication and mechanism of disease-causing differ significantly for each pathogen, eliciting a unique immune response in the host. Within this context, the MPS acts as both the sentinel and tailor of the immune system. As sentinels, MPS cells are found in blood and within tissues throughout the body to patrol against pathogenic insult. The strategy to detect 'microbial non-self' relies on MPS to recognize conserved microbial products known as 'pathogen-associated molecular pattern' (PAMPs). PAMPs recognition represents a checkpoint in the response to pathogens and relies on conserved 'pattern recognition receptors' (PRRs). Upon PRR engagement, MPS mount a cell-autonomous attack that includes the internalization and compartmentalization of intracellular pathogens into toxic compartments that promote destruction. In parallel, MPS cells launch an inflammatory response composed of a cellular arm and soluble factors to control extracellular pathogens. In cases when innate immunity fails to eliminate the invading microbe, MPS serves as a tailor to generate adaptive immunity for pathogen eradication and generation of "memory" cells
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Scooped by
Gilbert C FAURE
January 16, 2017 1:49 PM
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A team of scientists has created a genetic map of all possible receptors the human immune system might generate—also known as the immunome. The proje
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Scooped by
Gilbert C FAURE
January 11, 2017 9:36 AM
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Cell. 2016 Jun 16;165(7):1658-71. doi: 10.1016/j.cell.2016.04.049. Epub 2016 May 19. Research Support, Non-U.S. Gov't
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Scooped by
Gilbert C FAURE
January 9, 2017 9:01 AM
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If you want to learn more about my condition please watch House Season 1 episode 17: Role Model until you get it.... https://t.co/kt7SFR9GdR
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Scooped by
Gilbert C FAURE
January 8, 2017 1:21 PM
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Clin Rev Allergy Immunol. 2015 Dec;49(3):333-46. doi: 10.1007/s12016-014-8453-8. Review
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Scooped by
Gilbert C FAURE
January 7, 2017 3:29 PM
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Gattinoni and colleagues discuss the emerging roles of this subset of long-lived memory T lymphocytes, and highlight ways in which these cells might be exploited to achieve therapeutic aims.
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Scooped by
Gilbert C FAURE
January 7, 2017 6:54 AM
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Both genetics and environment affect the number and phenotype of immune cells. Here the authors characterize the degree of influence of genetics versus environment on various immune cell parameters by analysing a large cohort of female twins.
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Scooped by
Gilbert C FAURE
January 5, 2017 9:54 AM
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In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)–related diseases. Three patients presented with EBV-associated Hodgkin’s lymphoma and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27. Blood lymphocyte numbers were normal, but the proportions of memory B cells and EBV-specific effector memory CD8+ T cells were reduced. Furthermore, although T cell proliferation was normal, in vitro–generated EBV-specific cytotoxic T cell activity was reduced because of CD70 deficiency. This reflected impaired activation by, rather than effects during killing of, EBV-transformed B cells. Notably, expression of 2B4 and NKG2D, receptors implicated in controlling EBV infection, on memory CD8+ T cells from CD70-deficient individuals was reduced, consistent with their impaired killing of EBV-infected cells. Thus, autosomal recessive CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70–CD27 interactions therefore play a nonredundant role in T and B cell–mediated immunity, especially for protection against EBV and humoral immunity.
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Scooped by
Gilbert C FAURE
January 5, 2017 4:12 AM
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TCR Signaling and CD28/CTLA-4 Signaling Cooperatively Modulate T Regulatory Cell Homeostasis Michael P. Holt*, George A. Punkosdy†,‡, Deborah D. Glass* and Ethan M. Shevach* *Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,...
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Scooped by
Gilbert C FAURE
January 4, 2017 11:19 AM
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Autoimmun Rev. 2016 Sep;15(9):917-22. doi: 10.1016/j.autrev.2016.07.007. Epub 2016 Jul 5. Review
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Scooped by
Gilbert C FAURE
December 31, 2016 1:15 AM
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Editorial: HSPs—Ambiguous Mediators of Immunity
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Suggested by
LIGHTING
January 19, 2017 8:03 AM
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Tissue-resident memory T (TRM) cells, a population of noncirculating memory T cells, are one of the essential components of immunological memory in both mouse and human. Although CD69+CD103+ TRM cells represent a major TRM cell population in barrier tissues including the mucosal surface and the skin, CD69+CD103− TRM cells dominate most nonbarrier tissues, such as the kidney. TGF-β is required for the differentiation of CD69+CD103+ TRM cells in barrier tissues. However, the developmental control of CD69+CD103− TRM cells in nonbarrier tissues remains largely unknown and the involvement of TGF-β signaling is less clear. In this study we demonstrated that TGF-β promoted the formation of kidney-resident T cells via enhancing the tissue entry of effector T cells. Mechanistically, TGF-β enhanced E- and P-selectin and inflammatory chemokine-mediated extravasation of effector T cells. Thus TGF-β controls the first developmental checkpoint of TRM cell differentiation in nonbarrier tissues.
This article is featured in In This Issue , p.[555][1]
[1]: /lookup/volpage/198/555
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Suggested by
LIGHTING
January 18, 2017 8:51 AM
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Regulatory T (T reg) cells are essential for peripheral homeostasis and known to target and suppress dendritic cells (DCs). One important mechanism is through prolonged interaction between antigen-specific T reg cells and DCs that down-regulates the co-stimulatory capacity of DCs. However, the dynamics and TCR specificities of such T reg cell–DC interaction and its relevance to the suppressive outcomes for individual DCs have not been clarified. To gain insights into the underlying cellular events in vivo, we analyzed individual T reg cell–DC interaction events in lymph nodes by intravital microscopy. Our results show that, upon exposure to interleukin-2, T reg cells formed prolonged adhesive contact with DCs, independent of antigen or MHC recognition, which significantly suppressed the contemporaneous interaction of the same DCs with antigen-specific conventional T cells and impaired T cell priming. Therefore, T reg cells may function in part as feedback regulators in inflammatory milieu, by suppressing local DCs and interrupting immune activation in a contact-dependent and class II MHC-independent manner.
J Exp Med. 2017 Jan 12. pii: jem.20160629. doi: 10.1084/jem.20160629. [Epub ahead of print]
Via Denis Hudrisier
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Suggested by
LIGHTING
January 15, 2017 1:49 PM
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Mutations in human LPIN2 produce a disease known as Majeed syndrome, the clinical manifestations of which are ameliorated by strategies that block IL-1β or its receptor. However the role of lipin-2 during IL-1β production remains elusive. We show here that lipin-2 controls excessive IL-1β formation in primary human and mouse macrophages by several mechanisms, including activation of the inflammasome NLRP3. Lipin-2 regulates MAPK activation, which mediates synthesis of pro–IL-1β during inflammasome priming. Lipin-2 also inhibits the activation and sensitization of the purinergic receptor P2X7 and K+ efflux, apoptosis-associated speck-like protein with a CARD domain oligomerization, and caspase-1 processing, key events during inflammasome activation. Reduced levels of lipin-2 in macrophages lead to a decrease in cellular cholesterol levels. In fact, restoration of cholesterol concentrations in cells lacking lipin-2 decreases ion currents through the P2X7 receptor, and downstream events that drive IL-1β production. Furthermore, lipin-2–deficient mice exhibit increased sensitivity to high lipopolysaccharide doses. Collectively, our results unveil lipin-2 as a critical player in the negative regulation of NLRP3 inflammasome.
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Scooped by
Gilbert C FAURE
January 11, 2017 6:35 AM
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National Academy of Sciences
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Scooped by
Gilbert C FAURE
January 9, 2017 4:40 AM
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Generation of cellular heterogeneity is an essential feature of the adaptive immune system. This is best exemplified during humoral immune response when an expanding B cell clone assumes multiple cell fates, including class-switched B cells, antibody-secreting plasma cells, and memory B cells. Although each cell type is essential for immunity, their generation must be exquisitely controlled because a class-switched B cell cannot revert back to the parent isotype, and a terminally differentiated plasma cell cannot contribute to the memory pool. In this study, we show that an environmental sensor, the aryl hydrocarbon receptor (AhR) is highly induced upon B cell activation and serves a critical role in regulating activation-induced cell fate outcomes. We find that AhR negatively regulates class-switch recombination ex vivo by altering activation-induced cytidine deaminase expression. We further demonstrate that AhR suppresses class switching in vivo after influenza virus infection and immunization with model antigens. In addition, by regulating Blimp-1 expression via Bach2, AhR represses differentiation of B cells into plasmablasts ex vivo and antibody-secreting plasma cells in vivo. These experiments suggest that AhR serves as a molecular rheostat in B cells to brake the effector response, possibly to facilitate optimal recall responses. Thus, AhR might represent a novel molecular target for manipulation of B cell responses during vaccination.
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Scooped by
Gilbert C FAURE
January 8, 2017 3:39 AM
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A recent study from the Immunology Frontier Research Center (IFReC) in Japan led to the discovery of a new group of monocytes with a strange morphology tha
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Suggested by
Société Francaise d'Immunologie
January 7, 2017 7:01 AM
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Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that controlled an iNKT-cell lineage-specific gene-expression program and epigenetic landscape in a demethylase-activity-dependent manner. UTX-deficient iNKT cells exhibited impaired expression of iNKT cell signature genes due to a decrease in activation-associated H3K4me3 marks and an increase in repressive H3K27me3 marks within the promoters occupied by UTX. We found that JunB regulated iNKT cell development and that the expression of genes that were targets of both JunB and the iNKT cell master transcription factor PLZF was UTX dependent. We identified iNKT cell super-enhancers and demonstrated that UTX-mediated regulation of super-enhancer accessibility was a key mechanism for commitment to the iNKT cell lineage. Our findings reveal how UTX regulates the development of iNKT cells through multiple epigenetic mechanisms.
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Scooped by
Gilbert C FAURE
January 5, 2017 2:03 PM
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Plasma cells produce secreted antibodies and are thought to lack expression of the membrane-bound immunoglobulins that constitute B-cell receptors.
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Scooped by
Gilbert C FAURE
January 5, 2017 4:47 AM
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Birmingham’s International Convention Centre (ICC) has secured the European Society for Immunodeficiencies (ESID) Congress in 2020. The venue and the city won the bid over competing cities Brussels and Geneva.
The congress, which brings together the
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Scooped by
Gilbert C FAURE
January 4, 2017 11:28 AM
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Scooped by
Gilbert C FAURE
January 2, 2017 2:04 PM
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Guo et al. find that small-molecule RORγT antagonist treatment induces CD4+CD8+ thymocyte
apoptosis, skews the T cell repertoire, prevents autoreactive T cell development,
and delays autoimmune EAE progression. This work underscores the risk versus benefit
of targeting RORγT in clinical testing of RORγT inhibitors.
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