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Scooped by
Gilbert C FAURE
November 8, 2018 2:43 PM
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Homodimeric antibodies devoid of light chains have evolved multiple times through
convergent evolution, yet their specific immunological functions remain poorly understood. We survey the molecular and structural features of these antibodies, their immunological functions in host defense, and...
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Scooped by
Gilbert C FAURE
November 6, 2018 1:21 PM
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![Figure][1]
Immune protection relies on the capacity of neutrophils to infiltrate challenged tissues. Naive tissues, in contrast, are believed to remain free of these cells and protected from their toxic cargo. Here, we show that neutrophils are endowed with the capacity to infiltrate multiple tissues in the steady-state, a process that follows tissue-specific dynamics. By focusing in two particular tissues, the intestine and the lungs, we find that neutrophils infiltrating the intestine are engulfed by resident macrophages, resulting in repression of Il23 transcription, reduced G-CSF in plasma, and reinforced activity of distant bone marrow niches. In contrast, diurnal accumulation of neutrophils within the pulmonary vasculature influenced circadian transcription in the lungs. Neutrophil-influenced transcripts in this organ were associated with carcinogenesis and migration. Consistently, we found that neutrophils dictated the diurnal patterns of lung invasion by melanoma cells. Homeostatic infiltration of tissues unveils a facet of neutrophil biology that supports organ function, but can also instigate pathological states.
[1]: pending:yes
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Scooped by
Gilbert C FAURE
November 6, 2018 7:58 AM
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RNA has long been the neglected middle child of biomolecules, the go-between between DNA, which encodes the cell's instructions, and proteins, which carry them out. Increasingly, though, researchers are recognizing RNA as ...
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Rescooped by
Gilbert C FAURE
from Immunology and Biotherapies
November 5, 2018 3:37 AM
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Unlike other immune cells, the processes by which different NK cell subsets expand and are maintained are not well understood. Here, Wu et al. transplanted barcoded hematopoietic progenitor cells into rhesus macaques to follow the production, expansion, and maintenance of NK cells in the peripheral circulation for more than 4 years. They identified oligoclonal CD56−CD16+ NK cell populations that segregated into unique clones, expanding or contracting over time and expressing specific surface KIR molecules. Offering a compartmentalized view of NK cell maintenance, distinct mature CD56−CD16+ NK cell subpopulations were maintained through self-renewal, independent of differentiation from hematopoietic progenitors or less mature NK cells, even upon challenges representing moderate proliferative stress.
Natural killer (NK) cells recognize and eliminate infected and malignant cells. Their life histories are poorly understood, particularly in humans, due to lack of informative models and endogenous clonal markers. Here, we apply transplantation of barcoded rhesus macaque hematopoietic cells to interrogate the landscape of NK cell production, expansion, and life histories at a clonal level long term and after proliferative challenge. We identify oligoclonal populations of rhesus CD56−CD16+ NK cells that are characterized by marked expansions and contractions over time yet remained long-term clonally uncoupled from other hematopoietic lineages, including CD56+CD16− NK cells. Individual or groups of CD56−CD16+ expanded clones segregated with surface expression of specific killer immunoglobulin-like receptors. These clonally distinct NK cell subpopulation patterns persisted for more than 4 years, including after transient in vivo anti-CD16–mediated depletion and subsequent regeneration. Profound and sustained interleukin-15–mediated depletion was required to generate new oligoclonal CD56−CD16+ NK cells. Together, our results indicate that linear NK cell production from multipotent hematopoietic progenitors or less mature CD56+CD16− cells is negligible during homeostasis and moderate proliferative stress. In such settings, peripheral compartmentalized self-renewal can maintain the composition of distinct, differentiated NK cell subpopulations.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
November 3, 2018 4:14 AM
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Suggested by
Société Francaise d'Immunologie
October 31, 2018 2:45 PM
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Mollaoglu et al. use genetically engineered mouse models of non-small-cell lung cancer
(NSCLC) to define the relationship between lineage-defining transcription factors
and squamous NSCLC and adenocarcinoma, revealing that this interplay also determines
neutrophil recruitment. Depletion of tumor-associated neutrophils (TANs) reduced squamous
tumors and promoted adenocarcinoma features, suggesting that the immune microenvironment
might contribute to the nature of the tumor.
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Scooped by
Gilbert C FAURE
October 31, 2018 8:41 AM
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Hanging in front of the abdomen like an apron, the depot of visceral fat known as the omentum helps regulate immune responses.
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Scooped by
Gilbert C FAURE
October 30, 2018 3:16 PM
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Innate immune receptors, well known mediators of response to non-self-molecules and
inflammation, also act as mediators of immunity triggered by ‘damage-associated molecular
patterns’ (DAMPs). Pathogen-associated molecular patterns (PAMPs) cause inflammation in mammals and a rapid immune response...
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Scooped by
Gilbert C FAURE
October 30, 2018 2:00 PM
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Ferrando-Martinez et al., showed that SIV-specific follicular (f)CD8 T cells are observed in both intact and disorganised lymph node follicles, and accumulate
A longitudinal analysis of clonal evolution of tumors across multiple tissues identifies
a parallel selection model that explains the role of immune editing in controlling
metastatic growth.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
October 28, 2018 3:40 PM
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![Figure][1]
The mammalian lymphatic system consists of strategically located lymph nodes (LNs) embedded into a lymphatic vascular network. Mechanisms underlying development of this highly organized system are not fully understood. Using high-resolution imaging, we show that lymphoid tissue inducer (LTi) cells initially transmigrate from veins at LN development sites using gaps in venous mural coverage. This process is independent of lymphatic vasculature, but lymphatic vessels are indispensable for the transport of LTi cells that egress from blood capillaries elsewhere and serve as an essential LN expansion reservoir. At later stages, lymphatic collecting vessels ensure efficient LTi cell transport and formation of the LN capsule and subcapsular sinus. Perinodal lymphatics also promote local interstitial flow, which cooperates with lymphotoxin-β signaling to amplify stromal CXCL13 production and thereby promote LTi cell retention. Our data unify previous models of LN development by showing that lymphatics intervene at multiple points to assist LN expansion and identify a new role for mechanical forces in LN development.
[1]: pending:yes
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Scooped by
Gilbert C FAURE
October 28, 2018 12:49 PM
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Research at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) yielded new insights into the environment surrounding different types of lung tumors, and described how these complex cell ecosystems may in turn ultimately affect response to treatment. The results were published today in Immunity and featured on the print cover of the journal.
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Scooped by
Gilbert C FAURE
October 28, 2018 8:14 AM
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Chronic liver injury caused by infection, toxins, or other inflammatory conditions can lead to liver fibrosis. Several cytokines have been linked to liver fibrosis, and here, Fabre et al . define a role for the type 3 cytokines interleukin-17A (IL-17A) and IL-22 in driving transforming growth factor–β (TGF-β)–dependent fibrosis. They observed elevated levels of IL-17A and IL-22 in intrahepatic lymphocytes from patients with hepatitis. Hepatic stellate cells treated with IL-22 showed enhanced p38 mitogen-activated protein kinase–dependent TGF-β signaling. Liver-resident neutrophils and mast cells were identified as the primary sources of IL-17 in humans, and mouse studies showed that blockade of IL-17A and IL-22 could reduce fibrosis. Together, these findings define a role for type 3 cytokines in driving fibrosis during liver injury.
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Scooped by
Gilbert C FAURE
November 8, 2018 10:38 AM
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Scooped by
Gilbert C FAURE
November 6, 2018 12:09 PM
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Several NK cell subsets have been reported in humans and mice, but their heterogeneity
remains poorly characterized. Using high-throughput single-cell RNA-seq, Crinier et al.
provide conserved tissue-specific gene signatures of NK cells from spleen and blood
and identified two major NK cell subsets transcriptionally similar across organs and
species.
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Scooped by
Gilbert C FAURE
November 5, 2018 9:37 AM
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Scooped by
Gilbert C FAURE
November 3, 2018 3:29 PM
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Last year, a 26-year-old man receiving treatment for leukemia went to a Swiss hospital’s emergency room with a fever, a sore throat, and a cough, and was admitted. His condition worsened, and 17 days later, he died from severe complications of measles.
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Scooped by
Gilbert C FAURE
November 1, 2018 4:07 AM
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Immunosuppression is one hallmark of sepsis, decreasing the host response to the primary septic pathogens and/or secondary nosocomial infections. CD4 T cells and B cells are among the array of immune cells that experience reductions in number and function during sepsis. “Help” from follicular helper (Tfh) CD4 T cells to B cells is needed for productive and protective humoral immunity, but there is a paucity of data defining the effect of sepsis on a primary CD4 T cell-dependent B cell response. Using the cecal ligation and puncture (CLP) mouse model of sepsis induction, we observed reduced antibody production in mice challenged with influenza A virus or TNP-KLH in alum early (2 days) and late (30 days) after CLP surgery compared to mice subjected to sham surgery. To better understand how these CD4 T cell-dependent B cell responses were altered by a septic event, we immunized mice with a Complete Freund’s Adjuvant emulsion containing the MHC II-restricted peptide 2W1S56-68 coupled to the fluorochrome phycoerythrin (PE). Immunization with 2W1S-PE/CFA results in T cell-dependent B cell activation, giving us the ability to track defined populations of antigen-specific CD4 T cells and B cells responding to the same immunogen in the same mouse. Compared to sham mice, differentiation and class switching in PE-specific B cells were blunted in mice subjected to CLP surgery. Similarly, mice subjected to CLP had reduced expansion of 2W1S-specific T cells and Tfh differentiatio
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Scooped by
Gilbert C FAURE
October 31, 2018 12:49 PM
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Daniel et al. describe that the nuclear receptor PPARγ has a significant ligand-insensitive,
genome-bound fraction that affects local chromatin structure upon macrophage polarization.
Ligand-insensitive PPARγ mediates the expression of a hidden gene set upon repeated
IL-4 exposure, providing transcriptional memory and an epigenomic ratchet mechanism
to support progressive polarization.
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Scooped by
Gilbert C FAURE
October 30, 2018 3:18 PM
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The elevated expression of 17 immunity-related genes is associated with better outcomes among women with aggressive forms of estrogen receptor–negative breast cancer. Zhiyuan Hu from the University of North Carolina at Chapel Hill, USA, and colleagues identified the 17-gene set by analyzing a...
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Scooped by
Gilbert C FAURE
October 30, 2018 2:10 PM
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Systemic immunoglobulin light chain amyloidosis is a disease characterized by the tissue accumulation of amyloid fibrillar aggregates, which leads to organ dysfunction. This Primer discusses the molecular mechanisms of this form of amyloidosis and highlights management strategies that have improved quality of life and survival.
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Suggested by
LIGHTING
October 30, 2018 7:43 AM
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CD8+ T cells differentiate into multiple effector and memory subsets to carry out
immune clearance of infected and cancerous cells and provide long-term protection.
Recent research identified a CXCR5+Tcf1+Tim-3− subset that localizes in, or proximal
to, B cell follicles in secondary lymphoid organs of mice, non-human primates, and
humans, hereby termed follicular cytotoxic T (TFC) cells. With remarkable similarity
to follicular helper T (TFH) cells, TFC differentiation is dependent on transcription
factors E2A, Bcl6, and Tcf1, but inhibited by other regulators, including Blimp1,
Id2, and Id3.
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Scooped by
Gilbert C FAURE
October 28, 2018 3:48 PM
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Regulatory T (Treg) cells prevent autoimmunity by limiting immune responses and inflammation in the secondary lymphoid organs and nonlymphoid tissues. While unique subsets of Treg cells have been described in some nonlymphoid tissues, their relationship to Treg cells in secondary lymphoid organs and circulation remains unclear. Furthermore, it is possible that Treg cells from similar tissue types share largely similar properties. We have identified a short-lived effector Treg cell subset that expresses the α2 integrin, CD49b, and exhibits a unique tissue distribution, being abundant in peripheral blood, vasculature, skin, and skin-draining lymph nodes, but uncommon in the intestines and in viscera-draining lymph nodes. CD49b+ Treg cells, which display superior functionality revealed by in vitro and in vivo assays, appear to develop after multiple rounds of cell division and TCR-dependent activation. Accordingly, single-cell RNA-seq analysis placed these cells at the apex of the Treg developmental trajectory. These results shed light on the identity and development of a functionally potent subset of mature effector Treg cells that recirculate through and survey peripheral tissues.
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Scooped by
Gilbert C FAURE
October 28, 2018 12:52 PM
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Scooped by
Gilbert C FAURE
October 28, 2018 8:16 AM
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Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evoluti…
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