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Scooped by
Gilbert C FAURE
April 1, 2019 2:23 PM
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This Review summarizes recent advances in our understanding of neutralizing antibody responses to enveloped viruses with different pathogenesis and discusses how this information is used to inform design of vaccines, therapeutics and diagnostics.
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Suggested by
LIGHTING
April 1, 2019 7:17 AM
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Chimeric antigen receptors (CARs) promote antigen loss in tumour cells by trogocytosis, which results in T cell fratricide killing and exhaustion but can be counteracted by cooperative killing and combinatorial targeting.
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Scooped by
Gilbert C FAURE
March 30, 2019 1:15 PM
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Suggested by
Société Francaise d'Immunologie
March 30, 2019 5:59 AM
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Cassetta et al. identify a breast cancer tumor-associated macrophage (TAM) transcriptome that is different from those of monocytes and tissue-resident macrophages, and which is associated with shorter disease-specific survival, and they demonstrate crosstalk between tumor cells and TAMs via...
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Scooped by
Gilbert C FAURE
March 29, 2019 12:59 PM
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The autoimmune regulator (Aire) serves an essential function for T cell tolerance by promoting the “promiscuous” expression of tissue antigens in thymic epithelial cells. Aire is also detected in rare cells in peripheral lymphoid organs, but the identity of these cells is poorly understood. Here, we report that Aire protein–expressing cells in lymph nodes exhibit typical group 3 innate lymphoid cell (ILC3) characteristics such as lymphoid morphology, absence of “classical” hematopoietic lineage markers, and dependence on RORγt. Aire+ cells are more frequent among lineage-negative RORγt+ cells of peripheral lymph nodes as compared with mucosa-draining lymph nodes, display a unique Aire-dependent transcriptional signature, express high surface levels of MHCII and costimulatory molecules, and efficiently present an endogenously expressed model antigen to CD4+ T cells. These findings define a novel type of ILC3-like cells with potent APC features, suggesting that these cells serve a function in the control of T cell responses.
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Scooped by
Gilbert C FAURE
March 28, 2019 3:47 PM
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The human antibody repertoire against influenza virus is shaped by prior infection and vaccination.
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Scooped by
Gilbert C FAURE
March 25, 2019 3:30 PM
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Many skin diseases, including psoriasis and atopic dermatitis, have a neurogenic component.In this regard, bidirectional interactions between components of the nervous system and multiple target cell...
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Scooped by
Gilbert C FAURE
March 24, 2019 6:06 AM
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Staphylococcal enterotoxin B (SEB) and related superantigenic toxins produced by Staphylococcus aureus are potent activators of the immune system. These protein toxins bind to major histocompatibility complex (MHC) class II molecules and specific Vβ regions of T-cell receptors (TCRs),...
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Suggested by
Société Francaise d'Immunologie
March 19, 2019 3:36 PM
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The Scientist is bringing together a panel of experts to discuss their research and experiences in using systems immunology to gain new insights into immune responses to infection through single-cell data analysis, and into innate immune dysfunction in HIV infection.
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Scooped by
Gilbert C FAURE
March 19, 2019 5:44 AM
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Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement. Existing reference databases are incomplete, as shown by recent AIRR-seq studies that have inferred the existence of many previously unreported polymorphisms. Completing the documentation of genetic variation in germline gene databases is therefore of crucial importance. Lymphocyte receptor genes and alleles are currently assigned by the Immunoglobulins (IG), T cell Receptors (TR) and Major Histocompatibility (MH) Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS) and managed in IMGT®, the international ImMunoGeneTics information system® (IMGT). In 2017, the IMGT Group reached agreement with a group of AIRR-seq researchers on the principles of a process for identifying and naming inferred allelic sequences, for their incorporation into IMGT®. These researchers represented the AIRR Community, a network of over 30
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Scooped by
Gilbert C FAURE
March 18, 2019 9:07 AM
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In this Review, Erika Pearce and colleagues detail the metabolic changes that occur in the tumour microenvironment, explaining how these shape immune cell function at these sites. They highlight the potential of targeting these metabolic pathways to treat patients with cancer
Ion channels facilitate the movement of ions across the plasma and organellar membranes. A recent symposium brought together scientists who study ion channels and transporters in immune cells, which highlighted advances in this emerging field and served to chart new avenues for investigating the roles of ion channels in immunity.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
March 16, 2019 12:51 PM
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The immunological synapse (IS) is a superstructure formed during T cell activation at the zone of contact between T cells and dendritic cells (DCs). The IS includes specific molecular components in the T cell and DCs sides that may result in different functionality. Most of the studies on the IS have focused on the T cell side of this structure and, in contrast, the information available on the IS of DCs is sparse. Autophagy is a cellular process involved in the clearance of damaged proteins and organelles via lysosomal degradation. Mitophagy is the selective autophagy of damaged mitochondria. In this study, it is shown that IS formation induces clustering of mitochondria in the IS of DCs and partial depolarization of these organelles. At the IS of the DCs also accumulate autophagy and mitophagy markers, even when the kinase complex mTORC1, an inhibitor of the autophagy, is active. Together the results presented indicate that IS formation induces local clustering of mitochondria and mitophagy, which could be a homeostatic mechanism to control the quality of mitochondria in this region. The data underline the complexity of the regulatory mechanisms operating in the IS of DCs.
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Scooped by
Gilbert C FAURE
April 1, 2019 2:22 PM
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Suggested by
Société Francaise d'Immunologie
March 31, 2019 7:00 AM
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CLR/Card9 signaling is essential for antifungal immunity. Roth et al. have identified
the Vav family of proteins as key activators of the Card9/NF-kB pathway, essential
for CLR-induced inflammatory responses and host defense against fungi.
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Suggested by
Société Francaise d'Immunologie
March 30, 2019 5:59 AM
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This study examines the extent to which memory CD4+ T cells share immunosurveillance strategies with CD8+ resident memory T cells (TRM). After acute viral infection, memory CD4+ T cells predominantly used residence to survey nonlymphoid tissues, albeit not as stringently as observed for CD8+ T...
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Suggested by
Société Francaise d'Immunologie
March 29, 2019 2:17 PM
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Janela et al. find that during cutaneous bacterial infection, a minor subset of type
I conventional dendritic cells (cDC1s) control neutrophil recruitment to the inflamed
site and survival and function therein through the secretion of the cytokine VEGF-α.
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Rescooped by
Gilbert C FAURE
from Immunology and Biotherapies
March 29, 2019 5:37 AM
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The finding could explain why the body tolerates some microbes ― and lead to better treatments for chronic infections.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
March 28, 2019 3:45 PM
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T lymphocytes are powerful immune cells that can destroy tumors, but cancers have developed tricks to evade killing. Vodnala et al. found that potassium ions in the tumor microenvironment serve a dual role of influencing T cell effector function and stemness (see the Perspective by Baixauli Celda...
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Scooped by
Gilbert C FAURE
March 24, 2019 6:07 AM
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Cao et al. show that human papillomavirus-positive, head and neck squamous cell carcinoma patients are associated with better survival when T-cells are activated. This study suggests that viral infection may recruit immune effector cells and that it may activate PD-1 and CTLA-4 immunosuppressive...
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Scooped by
Gilbert C FAURE
March 19, 2019 3:40 PM
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Suggested by
Société Francaise d'Immunologie
March 19, 2019 3:36 PM
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Lymph fluid carries cells, debris and viruses to draining lymph nodes. Hickman and colleagues show that large viruses can enter lymph node conduits and gain access to dendritic cells positioned deep within lymph nodes for efficient presentation of antigen to CD8+ T cells.
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Scooped by
Gilbert C FAURE
March 19, 2019 5:42 AM
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Chemokines are small secreted proteins that orchestrate migration and positioning of immune cells within the tissues. Chemokines are essential for the function of the immune system. Accumulating evidence suggest that chemokines play important roles in tumor microenvironment. In this review we discuss an association of chemokine expression and activity within the tumor microenvironment with cancer outcome. We summarize regulation of immune cell recruitment into the tumor by chemokine-chemokine receptor interactions and describe evidence implicating chemokines in promotion of the “inflamed” immune-cell enriched tumor microenvironment. We review both tumor-promoting function of chemokines, such as regulation of tumor metastasis, and beneficial chemokine roles, including stimulation of anti-tumor immunity and response to immunotherapy. Finally, we discuss the therapeutic strategies target tumor-promoting chemokines or induce/deliver beneficial chemokines within the tumor focusing on pre-clinical studies and clinical trials going forward. The goal of this review is to provide insight into comprehensive role of chemokines and their receptors in tumor pathobiology and treatment.
Resident tissue macrophages (RTMs) reside in various tissue-specific niches during development. They evince microenvironment-directed phenotypes that support host defense and tissue homeostasis. Chakarov et al. used single-cell RNA sequencing and fate-mapping of murine lung RTMs to interrogate RTM-subset heterogeneity, interrelationships, and ontogeny (see the Perspective by Mildner and Yona). In addition to alveolar macrophages, they identified two different interstitial macrophage populations. One population mostly abutted nerve fibers; the other population preferentially localized near blood vessels and appeared to support vessel integrity and inhibit inflammatory cell infiltration into tissues.
Science , this issue p. [eaau0964][1]; see also p. [1154][2]
### INTRODUCTION
Resident tissue macrophages (RTMs) are a heterogeneous population of immune cells occupying multiple tissue niches and exhibiting microenvironment-specific phenotypes and functions. In certain tissues such as the brain, lung, and liver, embryonically derived RTMs maintain themselves by self-renewal, whereas others, including those in the gut, dermis, and pancreas, are replaced by monocytes, at levels that are tissue specific. Once they arrive in their tissue of residence, monocytes undergo extensive differentiation according to molecular cues provided by their distinct tissue-specific niches, enabling their development into specialized RTMs that support local tissue function.
### RATIONALE
As a result of this ontogenetic and tissue niche heterogeneity, each tissue contains multiple populations of macrophages. For example, in the murine lung, alveolar macrophages are the major embryonically derived population in the alveolar spaces, whereas a minor population named interstitial macrophages (IMs) resides within the lung parenchyma. Previous results reported several phenotypically distinct IM subpopulations, whose relationship remained unknown. Do they represent independent populations or, rather, different points on the spectrum of maturation and activation states? How do these differences relate to their localization in tissue or roles in tissue function in health and disease? Does such macrophage heterogeneity also exist in other tissues?
### RESULTS
Here, using single-cell mRNA sequencing, we unbiasedly identified two independent populations exhibiting distinct gene expression profiles and phenotypes: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) RTMs. We uncovered evidence of parallel populations in multiple others tissues, including the heart, fat, and dermis, as well as in human lung and omental and subcutaneous fat tissues, suggesting that a similar dichotomy is observed in human tissues.
We further demonstrated that both populations are slowly replaced by Ly6Chi monocytes. Importantly, using complementary fate-mapping models, we showed that monocyte-derived RTMs (MRTMs) are two separate lineages, rather than representing points along a developmental or maturation continuum. Notably, these distinct MRTM populations preferentially reside within different, but conserved, subtissular niches, located either adjacent to nerve bundles and fibers (Lyve1loMHCIIhi) or blood vessels (Lyve1hiMHCIIlo) across tissues.
Finally, by acutely depleting Lyve1hiMHCIIlo MRTMs using a mouse model of inducible macrophage depletion during the induction of fibrosis, we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung and heart fibrosis, demonstrating their critical role in tissue inflammation.
### CONCLUSION
Two independent MRTMs populations exist across tissues with specific niche-dependent phenotype and functional programming. Their different roles in homeostasis, immune regulation, and fibrosis renders them attractive and separate cellular targets for the therapeutic exploitation of RTM subsets.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
March 17, 2019 2:14 PM
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