Featured
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Article
| Open Access
FOXP3 recognizes microsatellites and bridges DNA through multimerization
FOXP3 uses the forkhead domain to form a higher-order multimer after binding to TnG repeat microsatellites.
- Wenxiang Zhang
- , Fangwei Leng
- & Sun Hur
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Article |
Latent human herpesvirus 6 is reactivated in CAR T cells
Genomics analyses reveal that in vitro culture of CAR T cells can lead to reactivation of a latent herpesvirus, which might be involved in complications in patients receiving associated cell therapies.
- Caleb A. Lareau
- , Yajie Yin
- & Ansuman T. Satpathy
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Article
| Open Access
Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency
Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases
- Tom Le Voyer
- , Audrey V. Parent
- & Anne Puel
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Article |
Thymic mimetic cells function beyond self-tolerance
Multiomic analyses of mouse thymic epithelial cells identify several unconventional subsets that are mimetics of various populations of terminally differentiated parenchymal cells and provide insights into their development, molecular features and function.
- Tal Givony
- , Dena Leshkowitz
- & Jakub Abramson
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Article
| Open Access
Dissecting human population variation in single-cell responses to SARS-CoV-2
Population differences in immune responses to SARS-CoV-2 can be explained by environmental exposures, but also by local adaptation acting through genetic variants acquired after admixture with archaic hominin forms.
- Yann Aquino
- , Aurélie Bisiaux
- & Lluis Quintana-Murci
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Article |
Africa-specific human genetic variation near CHD1L associates with HIV-1 load
Africa-specific genetic variation on chromosome 1 near CHD1L is associated with HIV replication in vivo.
- Paul J. McLaren
- , Immacolata Porreca
- & Jacques Fellay
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Article
| Open Access
A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection
The human leukocyte antigen allele HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection due to pre-existing T cell immunity.
- Danillo G. Augusto
- , Lawton D. Murdolo
- & Jill A. Hollenbach
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Article |
Autoimmunity in Down’s syndrome via cytokines, CD4 T cells and CD11c+ B cells
An autoimmune-prone state of steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation contributes to a breach in immune tolerance in individuals with Down’s syndrome.
- Louise Malle
- , Roosheel S. Patel
- & Dusan Bogunovic
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Article |
Common human genetic variants of APOE impact murine COVID-19 mortality
Mice bearing different variants of APOE exhibit different COVID-19 outcomes, with APOE2 and APOE4 associated with more severe disease, and this relationship between APOE genotype and disease severity is supported by clinical data in humans.
- Benjamin N. Ostendorf
- , Mira A. Patel
- & Sohail F. Tavazoie
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Article |
The retroelement Lx9 puts a brake on the immune response to virus infection
Experiments in mice show that a LINE-1 transposable element, Lx9c11, has a functional role in immunity by negatively regulating the response to viral infection to protect the host from an over-reactive immune response.
- Nenad Bartonicek
- , Romain Rouet
- & Cecile King
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Article
| Open Access
DOCK2 is involved in the host genetics and biology of severe COVID-19
A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.
- Ho Namkoong
- , Ryuya Edahiro
- & Yukinori Okada
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Article |
A genome-scale screen for synthetic drivers of T cell proliferation
A genome-scale gain-of-function screen using overexpression of nearly 12,000 open reading frames (ORFs) identifies positive regulators of human T cell function and suggests that ORF-based screens could be applied clinically to improve T cell therapies.
- Mateusz Legut
- , Zoran Gajic
- & Neville E. Sanjana
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Article |
Genome-wide enhancer maps link risk variants to disease genes
Mapping enhancer regulation across human cell types and tissues illuminates genome function and provides a resource to connect risk variants for common diseases to their molecular and cellular functions.
- Joseph Nasser
- , Drew T. Bergman
- & Jesse M. Engreitz
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Article |
A myeloid–stromal niche and gp130 rescue in NOD2-driven Crohn’s disease
NOD2 deficiency drives fibrosis and stricturing complications in Crohn’s disease through dysregulated homeostasis of activated fibroblasts and macrophages, which is ameliorated by gp130 blockade in human cell and zebrafish models.
- Shikha Nayar
- , Joshua K. Morrison
- & Judy H. Cho
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Article |
Genetic mechanisms of critical illness in COVID-19
A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.
- Erola Pairo-Castineira
- , Sara Clohisey
- & J. Kenneth Baillie
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Article |
A distal enhancer at risk locus 11q13.5 promotes suppression of colitis by Treg cells
Shared synteny guides loss-of-function analysis of human enhancer homologues in mice, identifying a distal enhancer at the autoimmune and allergic disease risk locus at chromosome 11q13.5 whose function in regulatory T cells provides a mechanistic basis for its role in disease.
- Rabab Nasrallah
- , Charlotte J. Imianowski
- & Rahul Roychoudhuri
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Article |
CRISPR screen in regulatory T cells reveals modulators of Foxp3
A CRISPR-based screening platform was used to identify previously uncharacterized genes that regulate the regulatory T cell-specific master transcription factor Foxp3, indicating that this screening method may be broadly applicable for the discovery of other genes involved in autoimmunity and immune responses to cancer.
- Jessica T. Cortez
- , Elena Montauti
- & Deyu Fang
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Review Article |
Pathway paradigms revealed from the genetics of inflammatory bowel disease
This Review examines inflammatory bowel disease in the context of human genetics studies that help to identify pathways that regulate homeostasis of the mucosal immune system and discusses future prospects for disease-subtype classification and therapeutic intervention.
- Daniel B. Graham
- & Ramnik J. Xavier
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Article |
A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1
A dominantly inherited human autoinflammatory disease caused by mutations in RIPK1 is identified, and RIPK1 mutations that prevent caspase-8 cleavage sensitize cells to apoptosis, necroptosis and inflammation.
- Panfeng Tao
- , Jinqiao Sun
- & Qing Zhou
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Letter |
High frequency of shared clonotypes in human B cell receptor repertoires
Many clonotypes in human B cell repertoires are shared, including between adult and umbilical cord blood repertoires, which indicates that this similarity is not driven only by exposure to common antigens.
- Cinque Soto
- , Robin G. Bombardi
- & James E. Crowe Jr
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Article |
Gene expression variability across cells and species shapes innate immunity
Comparison of transcriptomic data from immune-stimulated cells across different species sheds light on the architecture of the innate immune response.
- Tzachi Hagai
- , Xi Chen
- & Sarah A. Teichmann
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Article |
Fine-mapping inflammatory bowel disease loci to single-variant resolution
Results of fine-mapping 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals and several new fine-mapping methods.
- Hailiang Huang
- , Ming Fang
- & Jeffrey C. Barrett
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Letter |
Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease
Complement-activating glycosylceramide-specific autoantibodies drive a self-propagating cycle of glycosylceramide accumulation and inflammation in Gaucher disease.
- Manoj K. Pandey
- , Thomas A. Burrow
- & Gregory A. Grabowski
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Letter |
A mechanism for expansion of regulatory T-cell repertoire and its role in self-tolerance
Regulatory T cells need to express a diverse T-cell-receptor repertoire to control pathogenic self-reactive T cells; here it is shown that repertoire diversification depends on the intronic Foxp3 enhancer CNS3 acting at the regulatory T-cell-precursor stage to induce T-cell-receptor responsiveness to low-strength signals.
- Yongqiang Feng
- , Joris van der Veeken
- & Alexander Y. Rudensky
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Letter |
Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11
Schlafen proteins are produced in response to interferon signalling, which can be activated by retroviral infection; this study shows that human schlafen 11 inhibits the late stages of HIV-1 production by binding non-specifically to tRNAs, thus preventing the expression of viral proteins.
- Manqing Li
- , Elaine Kao
- & Michael David
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Letter |
Structural and genetic basis for development of broadly neutralizing influenza antibodies
The events leading to the generation of broadly neutralizing antibodies to influenza viruses, which may hold the key to developing a universal flu vaccine, are elucidated.
- Daniel Lingwood
- , Patrick M. McTamney
- & Gary J. Nabel
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Letter |
Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development
The binding of angiopoietin-like proteins to immune-inhibitory receptors maintains ‘stemness’ of haematopoietic stem cells and supports leukaemia development.
- Junke Zheng
- , Masato Umikawa
- & Cheng Cheng Zhang
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Letter |
PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells
T regulatory (Treg) cells in visceral adipose tissue express high levels of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-γ, and fat-specific adaptation of Treg cells is dependent on PPAR-γ.
- Daniela Cipolletta
- , Markus Feuerer
- & Diane Mathis
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Outlook |
Morbidity: A personal response
Some people get horribly sick from the flu, and even die. Others just rest for a few days. What's behind this fateful variation?
- Christine Junge
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News |
Cod genome reveals unusual immune system
Missing molecules show evolutionary flexibility, and may help fish farmers.
- George Wigmore
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Letter |
A genetically humanized mouse model for hepatitis C virus infection
- Marcus Dorner
- , Joshua A. Horwitz
- & Alexander Ploss
Base-editing mutagenesis maps alleles to tune human T cell functions