Top 10 Biorxiv Papers Today in Immunology


2.029 Mikeys
#1. Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians
Kosuke Hashimoto, Tsukasa Kouno, Tomokatsu Ikawa, Norihito Hayatsu, Yurina Miyajima, Haruka Yabukami, Tommy Terooatea, Takashi Sasaki, Takahiro Suzuki, Matthew Valentine, Giovanni Pascarella, Yasushi Okazaki, Harukazu Suzuki, Jay W Shin, Aki Minoda, Ichiro Taniuchi, Hideyuki Okano, Yasumichi Arai, Nobuyoshi Hirose, Piero Carninci
Supercentenarians, people who have reached 110 years of age, are a great model of healthy aging. Their characteristics of delayed onset of age-related diseases and compression of morbidity imply that their immune system remains functional. Here we performed single-cell transcriptome analysis of 61,202 peripheral blood mononuclear cells (PBMCs), derived from seven supercentenarians and five younger controls. We identified a marked increase of cytotoxic CD4 T-cells (CD4 CTLs) coupled with a substantial reduction of B-cells as a novel signature of supercentenarians. Furthermore, single-cell T-cell receptor sequencing of two supercentenarians revealed that CD4 CTLs had accumulated through massive clonal expansion, with the most frequent clonotypes accounting for 15% to 35% of the entire CD4 T-cell population. The CD4 CTLs exhibited substantial heterogeneity in their degree of cytotoxicity as well as a nearly identical transcriptome to that of CD8 CTLs. This indicates that CD4 CTLs utilize the transcriptional program of the CD8 lineage...
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biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #bioRxiv
biorxiv_immuno: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/deT1JQzJWV #biorxiv_immuno
PromPreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/rpu4u6qeU3
thparietallobe: RT @biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #…
skirchmaier: RT @biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #…
ybazetag: RT @biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #…
_Daniel_Vera: RT @biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #…
EndeavorBio: RT @biorxiv_immuno: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/deT1JQzJWV #b…
InflammatoryDC: RT @biorxiv_immuno: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/deT1JQzJWV #b…
ZebraFishLab: RT @biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #…
rjmiragaia: RT @biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #…
TheEugenest: RT @biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #…
genolib_19: RT @biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #…
SimSci9: RT @biorxivpreprint: Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians https://t.co/xlruUVwgQx #…
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Authors: 20
Total Words: 11023
Unqiue Words: 3307

2.027 Mikeys
#2. Histone acetylome-wide association study of tuberculosis
Ricardo C.H. del Rosario, Jeremie Poschmann, Pavanish Kumar, Catherine Y. Cheng, Seow Theng Ong, Hajira Shreen Hajan, Dilip Kumar, Mardiana Marzuki, Xiaohua Lu, Andrea Lee, Yanxia Tang, Cynthia Bin Eng Chee, Carey Lim, Bernett Lee, Josephine Lum, Francesca Zolezzi, Michael Poidinger, Olaf Rotzschke, Chiea Chuen Khor, Yee T. Wang, K. George Chandy, Gennaro De Libero, Amit Singhal, Shyam Prabhakar
Host-cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis ( Mtb ) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Chinese discovery cohort, which were validated in a subsequent multi-ethnic cohort, thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression in a third cohort. Differential acetylation was enriched near potassium channel genes, including KCNJ15 , which modulated Akt-mTOR signaling and promoted Mtb clearance in vitro . We performed histone acetylation QTL analysis on the dataset and identified candidate causal variants for immune phenotypes. Our study serves as proof-of-principle for HAWAS to...
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biorxivpreprint: Histone acetylome-wide association study of tuberculosis https://t.co/Ku5vfyAfu8 #bioRxiv
biorxiv_immuno: Histone acetylome-wide association study of tuberculosis https://t.co/MFxGyPPtv3 #biorxiv_immuno
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Authors: 24
Total Words: 0
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2.026 Mikeys
#3. Comparison of IL-33 and IL-5 Family Mediated Activation of Human Eosinophils
Evelyn L Angulo, Elizabeth M McKernan, Paul S Fichtinger, Sameer K Mathur
Eosinophils are the prominent inflammatory cell involved in allergic asthma, atopic dermatitis, eosinophilic esophagitis, and hypereosinophilic syndrome and are found in high numbers in local tissue and/or circulating blood of affected patients. There is recent interest in a family of alarmins, including TSLP, IL-25 and IL-33, that are epithelial-derived and released upon stimulation of epithelial cells. Several genome wide association studies have found SNPs in genes encoding IL-33 to be risk factors for asthma. In two studies examining the direct role of IL-33 in eosinophils, there were differences in eosinophil responses. We sought to further characterize activation of eosinophils with IL-33 compared to activation by other cytokines and chemokines. We assessed IL-33 stimulated adhesion, degranulation, chemotaxis and cell surface protein expression in comparison to IL-3, IL-5, and eotaxin-1 on human eosinophils. Our results demonstrate that IL-33 can produce as potent or more eosinophil activation than IL-3, IL-5 and eotaxin-1....
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biorxivpreprint: Comparison of IL-33 and IL-5 Family Mediated Activation of Human Eosinophils https://t.co/QG4eDUUN9Z #bioRxiv
biorxiv_immuno: Comparison of IL-33 and IL-5 Family Mediated Activation of Human Eosinophils https://t.co/9DwHIMugyd #biorxiv_immuno
sbotlite: RT @biorxivpreprint: Comparison of IL-33 and IL-5 Family Mediated Activation of Human Eosinophils https://t.co/QG4eDUUN9Z #bioRxiv
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Authors: 4
Total Words: 0
Unqiue Words: 0

2.009 Mikeys
#4. Fcrl5 and T-bet define influenza-specific memory B cells that predict long-lived antibody responses
Anoma Nellore, Christopher D Scharer, Rodney G King, Christopher M Tipton, Esther Zumaquero, Christopher Fucile, Betty Mousseau, John E Bradley, Kevin Macon, Tian Mi, Paul A Goepfert, John F Kearney, Jeremy M Boss, Troy D Randall, Ignacio Sanz, Alexander Rosenberg, Frances E Lund
Early surrogates for long-lived immunity after inactivated influenza vaccination (IIV) are lacking. Antigen-specific memory B cells (Bmem) after IIV have been recently identified. We show that the antigen-specific Bmem compartment after IIV is heterogenous and comprises a clonotypically and transcriptionally distinct T-bethi subset that persists in circulation over time after vaccination and exclusively correlates with the long-lived antibody response. We demonstrate that this subset has an effector memory transcriptome and is epigenetically remodeled to facilitate intracellular immunoglobulin production. Finally, via clonal sharing, we show an enriched in vivo ontologic relationship between the secondary plasmablast response that develops after vaccine boost and the T-bethi fraction of the flu-specific Bmem response that forms after initial prime. Collectively, our data identify a novel biomarker of durable humoral immunity after influenza vaccination.
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biorxivpreprint: Fcrl5 and T-bet define influenza-specific memory B cells that predict long-lived antibody responses https://t.co/P8RB7DasqY #bioRxiv
biorxiv_immuno: Fcrl5 and T-bet define influenza-specific memory B cells that predict long-lived antibody responses https://t.co/TUaNtyNq7g #biorxiv_immuno
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Sample Sizes : [5, 2, 5, 3, 4, 4, 5]
Authors: 17
Total Words: 19759
Unqiue Words: 5693

1.997 Mikeys
#5. Male sex exacerbates the plasticity and pathogenicity of Th17 cells in a chronic model of CNS autoimmunity.
Prenitha Mercy Ignatius Arokia Doss, Joanie Baillargeon, Asmita Pradeep Yeola, John B Williams, Mickael Leclercq, Charles Joly-Beauparlant, Melanie Alpaugh, Ana C Anderson, Arnaud Droit, Hans Lassmann, Craig S Moore, Manu Rangachari
Sex differences in the incidence and severity of multiple sclerosis (MS) have long been recognized, but the underlying mechanisms remain poorly defined. Here, we elucidate the cellular and molecular underpinnings of why male sex is associated with a more aggressive and debilitating disease course. Using an adoptive transfer model of EAE to examine disease driven by CD4+ T helper 17 (Th17 cells), we find that male Th17 cells induced disease of increased severity relative to female Th17 cells, irrespective of whether the cells were transferred to male or female recipients. Both female and male peripheral Th17 exhibited phenotypic plasticity as early as disease onset, producing either IL-17 and IFNγ together or IFNγ alone; however, a higher proportion of male Th17 produced IFNγ throughout the disease course, with increased expression of both IFNγ and GM-CSF from CNS-infiltrating Th17 cells correlating with severe disease in males. Further, male cells upregulated signature genes previously associated with phenotypically plastic Th17...
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Sample Sizes : [4, 5, 8, 6, 7, 6, 8, 5, 12, 7, 5, 3, 14, 4, 5, 5, 3, 6, 8, 4, 4, 5, 6, 3, 3, 3, 5, 12, 14, 4, 4, 4, 3]
Authors: 12
Total Words: 17661
Unqiue Words: 4323

1.996 Mikeys
#6. Single cell RNA-seq in regenerative and fibrotic biomaterial environments defines new macrophage subsets
Sven D Sommerfeld, Christopher Cherry, Remi M Schwab, Liam Chung, David R Maestas, Philippe Laffont, Julie E Stein, Ada Tam, Franck Housseau, Janice M Taube, Drew M Pardoll, Patrick Cahan, Jennifer H Elisseeff
Macrophages play diverse roles in the immune response to infection, cancer, and wound healing where they respond to local environmental signals, yet identification and phenotypic characterization of functional subsets in vivo remains limited. We performed single cell RNA sequencing analysis on differentiated macrophages sorted from a biologic matrix-induced regenerative environment versus a synthetic biomaterial foreign body response (FBR), characterized by TH2/interleukin (IL)-4 and TH17/IL-17, respectively. In the regenerative environment, unbiased clustering and pseudo time analysis revealed distinct macrophage subsets responsible for antigen presentation, chemoattraction, and phagocytosis, as well as a small population with expression profiles of both dendritic cells and skeletal muscle. In the FBR environment, we identified a CD9hi+IL-36γ+ macrophage subset that expressed TH17-associated molecules characteristic of certain auto-immune responses that were virtually absent in mice lacking the IL-17 receptor. Surface marker...
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Authors: 13
Total Words: 8731
Unqiue Words: 2462

1.996 Mikeys
#7. Thymically-derived Foxp3+ regulatory T cells are the primary regulators of type 1 diabetes in the non-obese diabetic mouse model
Daniel R Holohan, Frédéric Van Gool, Jeffrey A Bluestone
Regulatory T cells (Tregs) are an immunosuppressive population that are identified based on the stable expression of the fate-determining transcription factor forkhead box P3 (Foxp3). Tregs can be divided into distinct subsets based on whether they developed in the thymus (tTregs) or in the periphery (pTregs). Whether there are unique functional roles that distinguish pTregs and tTregs remains largely unclear. To elucidate these functions, efforts have been made to specifically identify and modify individual Treg subsets. Deletion of the conserved non-coding sequence (CNS)1 in the Foxp3 locus leads to selective impairment of pTreg generation without disrupting tTreg generation in the C57BL/6J background. Using CRISPR-Cas9 genome editing technology, we removed the Foxp3 CNS1 region in the non-obese diabetic (NOD) mouse model of spontaneous type 1 diabetes mellitus (T1D) to determine if pTregs contribute to autoimmune regulation. Deletion of CNS1 impaired in vitro induction of Foxp3 in naïve NOD CD4+ T cells, but it did not alter...
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Authors: 3
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1.996 Mikeys
#8. CD8+ T cell immunity is compromised by anti-CD20 treatment and rescued by IL-17A
Facundo Fiocca Vernengo, Cristian G. Beccaria, Cintia L. Araujo Furlan, Jimena Tosello Boari, Laura Almada, Melisa Gorosito Serran, Yamila Gazzoni, Carolina L. Montes, Eva Acosta Rodriguez, Adriana Gruppi
Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8+ T cell immunity using an experimental model of Trypanosoma cruzi infection, in which CD8+ T cells play a pivotal role. C57BL/6 mice were treated with anti-CD20 for B cell depletion prior to T. cruzi infection. Infected anti-CD20-treated mice exhibited a CD8+ T cell response with a conserved expansion phase followed by an early contraction, resulting in a strong reduction in total and parasite-specific CD8+ T cells at 20 days postinfection. Anti-CD20 injection decreased the number of effector and memory CD8+ T cells and reduced the frequency of proliferating and cytokine-producing CD8+ T cells. Accordingly, infected anti-CD20-treated mice presented lower cytotoxicity of T. cruzi peptide-pulsed target cells in vivo. All of these alterations in CD8+ T cell immunity were associated with increased tissue parasitism....
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Sample Sizes : [4, 4, 4]
Authors: 10
Total Words: 11457
Unqiue Words: 3476

1.995 Mikeys
#9. Extracting T Cell Function and Differentiation Characteristics from the Biomedical Literature
Eric Allen Czech, Jeffrey Hammerbacher
The role of many cytokines and transcription factors in the function and development of human T cells has been the subject of extensive research, however much of this work only demonstrates experimental findings for a relatively small portion of the molecular signaling network that enables the plasticity inherent to these cells. We apply recent advancements in methods for weak supervision of natural language models to aid in extracting these individual findings, as ~400k cell type, cytokine, and transcription factor relations from ~10k full-text PMC articles, before collating them as freely available datasets, analysis and source code available at https://github.com/hammerlab/t-cell-relation-extraction.
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InflammatoryDC: RT @biorxiv_immuno: Extracting T Cell Function and Differentiation Characteristics from the Biomedical Literature https://t.co/yB7t5tgv9T…
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Authors: 2
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1.994 Mikeys
#10. Cervical gene delivery of the antimicrobial peptide, Human β-defensin (HBD)-3, in a mouse model of ascending infection-related preterm birth
Natalie Suff, Rajvinder Karda, Juan Antinao Diaz, Ng Joanne, Baruteau Julian, Dany Perocheau, Peter W. Taylor, Dagmar Alber, Suzanne M.K. Buckley, Mona Bajaj-Elliott, Simon N Waddington, Donald Peebles
Approximately 40% of preterm births are preceded by microbial invasion of the intrauterine space: ascent from the vagina is the most common pathway. Within the cervical canal, antimicrobial peptides and proteins (AMPs) help to constitute a barrier which prevents ascending infection. We investigated whether expression of the AMP, human β-defensin-3 (HBD3), in the cervical mucosa prevented bacterial ascent from the vagina into the uterine cavity of pregnant mice. An adeno-associated virus vector containing both the HBD3 gene and GFP transgene (AAV8 HBD3.GFP) or control (AAV8 GFP), was administered intravaginally into E13.5 pregnant mice. Ascending infection was induced at E16.5 using bioluminescent E.coli (E.coli K1 A192PP-lux2). Bioluminescence imaging showed bacterial ascent into the uterine cavity, cellular events that led to premature delivery and a reduction in pups born alive, compared with uninfected controls. In addition, a significant reduction in uterine bioluminescence in the AAV8 HBD3.GFP-treated mice was observed 24...
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Authors: 12
Total Words: 11409
Unqiue Words: 3141

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