Top 5 Biorxiv Papers Today in Immunology


2.012 Mikeys
#1. Peripheral blood cell immunophenotyping reveals distinct subgroups of inflamed depression
Mary-Ellen Lynall, Lorinda Turner, Junaid Bhatti, Jonathan Cavanagh, Peter De Boer, Valeria Mondelli, Declan Jones, Wayne Drevets, Philip Cowen, Neil Harrison, Carmine Maria Pariante, Linda Pointon, NIMA Consortium, Menna Clatworthy, Edward Bullmore
Depression has been associated with increased inflammatory proteins but changes in circulating immune cells are less well defined. We used multi-parametric flow cytometry to investigate 14 subsets of peripheral blood cells in 206 cases of major depressive disorder (MDD) and 77 age- and sex-matched controls. There were significant case-control differences, by univariate and multivariate analysis: cases showed increased immune cell counts, especially neutrophils, CD4+ T cells and monocytes, and increased inflammatory proteins (C-reactive protein and interleukin-6). Within-group analysis demonstrated significant association between the severity of depressive symptoms and increased myeloid and CD4+ cell counts. MDD cases could be partitioned into two groups by forced binary clustering of cell counts: the inflamed depression group (N=81 out of 206; 39%) had increased monocyte, CD4+ and neutrophil counts, increased C-reactive protein (CRP) and interleukin 6 (IL-6), and was more depressed than the uninflamed majority of cases. Relaxing...
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edbullmore: Analysis of white blood cell counts (N=206) finds two sub-groups of inflamed depression. Groups 2 and 3 (see fig) are more depressed (high HAMD) and more inflamed (high CRP/IL6) but have different myeloid/lymphoid cell profiles. @MLynall @NIMAconsortium https://t.co/3VJiaTOnd1 https://t.co/HnpKBAHtbR
edbullmore: White blood cell counts are increased in depression, and it is not always the same type of immune cells implicated, suggesting there may be more than one pathway to "inflamed depression" @MLynall @ClatworthyLab @psychiatry_ucam @NIMAConsortium @mrc https://t.co/3VJiaTOnd1
LabWaggoner: RT @biorxiv_immuno: Peripheral blood cell immunophenotyping reveals distinct subgroups of inflamed depression https://t.co/qNWi83uerU #bio…
Inannamarduk: RT @biorxivpreprint: Peripheral blood cell immunophenotyping reveals distinct subgroups of inflamed depression https://t.co/uDrpEJaJkG #bi…
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1.998 Mikeys
#2. MATE-Seq: Microfluidic Antigen-TCR Engagement Sequencing
Alphonsus HC Ng, Songming Peng, Alexander M Xu, Won Jun Noh, Katherine Guo, Michael T Bethune, William Chour, Jongchan Choi, Sung Yang, David Baltimore, James R Heath
Adaptive immunity is based on peptide antigen recognition. Our ability to harness the immune system for therapeutic gain relies on the discovery of the T cell receptor (TCR) genes that selectively target antigens from infections, mutated proteins, and foreign agents. Here we present a method that selectively labels peptide antigen-specific CD8+ T-cells in human blood using magnetic nanoparticles functionalized with peptide-MHC tetramers, isolates these specific cells within an integrated microfluidic device, and directly amplifies the TCR genes for sequencing. Critically, the identity of the peptide recognized by the TCR is preserved, providing the link between peptide and gene. The platform requires inputs on the order of just 100,000 CD8+ T cells, can be multiplexed for simultaneous analysis of multiple peptides, and performs sorting and isolation on chip. We demonstrate 1000-fold sensitivity enhancement of antigen-specific T-cell receptor detection and simultaneous capture of two virus antigen-specific T-cell receptors from...
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Inannamarduk: RT @biorxivpreprint: MATE-Seq: Microfluidic Antigen-TCR Engagement Sequencing https://t.co/e5OAT2q1TC #bioRxiv
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1.996 Mikeys
#3. Thera-SAbDab: the Therapeutic Structural Antibody Database
Matthew I J Raybould, Claire Marks, Alan P Lewis, Jiye Shi, Alexander Bujotzek, Bruck Taddese, Charlotte Deane
The Therapeutic Structural Antibody Database (Thera-SabDab; http://opig.stats.ox.ac.uk/webapps/therasabdab) tracks all antibody- and nanobody-related therapeutics recognised by the World Health Organisation (WHO), and identifies any corresponding structures in the Structural Antibody Database (SAbDab) with near-exact or exact variable domain sequence matches. Thera-SAbDab is synchronised with SAbDab to up-date weekly, reflecting new Protein Data Bank entries and the availability of new sequence data published by the WHO. Each therapeutic summary page lists structural coverage (with links to the appropriate SAbDab entries), alignments showing where any near-matches deviate in sequence, and accompanying metadata, such as intended target and investigated conditions. Thera-SAbDab can be queried by therapeutic name, by a combination of metadata, or by variable domain sequence - returning all therapeutics that are within a specified sequence identity over a specified region of the query. The sequences of all therapeutics listed in...
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1.996 Mikeys
#4. Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance
Radhika R Gudi, Subha Karumuthil-Melethil, Nicolas Perez, Gongbo Li, Chenthamarakshan Vasu
Inhibitory/repressor-receptors are upregulated significantly on activated T cells, and have been the molecules of attention as targets for inducing immune tolerance. Induction of effective antigen specific tolerance depends on concurrent engagement of the TCR and one or more of these inhibitory receptors. Here, we show, for the first time that dendritic cells (DCs) can be efficiently engineered to express multiple T cell inhibitory ligands, and enhanced engagement of T cell inhibitory receptors, upon antigen presentation, by these DCs can induce effective CD4+ T cell tolerance and suppress autoimmunity. Compared to control DCs, antigen presentation by DCs that ectopically express CTLA4, PD1 and BTLA selective ligands (B7.1wa, PD-L1, and HVEM-CRD1 respectively) individually (mono-ligand DCs) or in combination (multi-ligand DCs) causes an inhibition of CD4+ T cell proliferation and pro-inflammatory cytokine response, as well as increase in Foxp3+ Treg frequency and immune regulatory cytokine production. Administration of...
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Authors: 5
Total Words: 13073
Unqiue Words: 3038

1.996 Mikeys
#5. Simultaneous mRNA and protein quantification at the single-cell level delineates trajectories of CD4+ T-cell differentiation
Dominik Trzupek, Melanie Dunstan, Antony J Cutler, Mercede Lee, Leila Godfrey, Dominik Aschenbrenner, Holm H Uhlig, Linda Wicker, John A Todd, Ricardo C Ferreira
The transcriptomic and proteomic characterisation of CD4+ T cells at the single-cell level has been performed traditionally by two largely exclusive types of technologies: single cell RNA-sequencing (scRNA-seq) technologies and antibody-based cytometry. Here we demonstrate that the simultaneous targeted quantification of mRNA and protein expression in single-cells provides a high-resolution map of human primary CD4+ T cells, and reveals precise trajectories of canonical T-cell lineage differentiation in blood and tissue. We report modest correlation between mRNA and protein in primary CD4+ T cells at the single-cell level, highlighting the importance of including quantitative protein expression data to characterise cell effector function. This approach provides a massively-parallel, cost-effective, solution to dissect the heterogeneity of immune cell populations and is ideally suited for the detailed immunophenotypic characterisation of rare and potentially pathogenic immune subsets. This transcriptomic and proteomic hybrid...
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