Research Highlight |
Featured
-
-
News & Views |
TREM1 is the new kid on the block for the aging-associated innate immune response and Alzheimer’s disease
The immunometabolism of microglia determines not only their own fate but also that of neurons and their function during aging and neurodegeneration.
- Michael T. Heneka
-
Research Briefing |
Two rare UNC93B1 variants contribute to childhood-onset lupus
This work identifies two rare genetic variants of UNC93B1 that contribute to the development of childhood-onset lupus. Mice that expressed one of these variants developed a lupus-like disease. UNC93B1 is known to regulate the localization of Toll-like receptors (TLRs) to the endosome, and UNC93B1 variants resulted in enhanced responses to TLR7 and TLR8 agonists.
-
Article
| Open Access
Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus
Rare genetic variants in UNC93B1 predispose to childhood-onset lupus via TLR7/-8–IRAK1/-4, validated with a corresponding mouse model.
- Mahmoud Al-Azab
- , Elina Idiiatullina
- & Seth L. Masters
-
Article
| Open Access
Vaccination induces broadly neutralizing antibody precursors to HIV gp41
Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.
- Torben Schiffner
- , Ivy Phung
- & William R. Schief
-
Resource
| Open Access
Nociceptor-immune interactomes reveal insult-specific immune signatures of pain
Woolf and colleagues use single-cell transcriptomics to determine the gene signature of infiltrating immune cells and potential cell–cell interactions between receptors, ligands, ion channels and metabolites expressed on immune cells and sensory neurons in three models of pain.
- Aakanksha Jain
- , Benjamin M. Gyori
- & Clifford J. Woolf
-
Article
| Open Access
Perinatal thymic-derived CD8αβ-expressing γδ T cells are innate IFN-γ producers that expand in IL-7R–STAT5B-driven neoplasms
Here the authors identify and characterize the development and function of an IFN-γ-producing CD8αβ+ subset of γδ T cells that contributes to malignancy.
- Nital Sumaria
- , Gina J. Fiala
- & Bruno Silva-Santos
-
Article |
A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice
CAR T cells have shown great promise in treating some cancers and are now being applied to other diseases. Here the authors engineer mouse and human T cells and show that a single infusion can result in lasting remission from asthma in mice.
- Gang Jin
- , Yanyan Liu
- & Min Peng
-
Meeting Report |
Leveraging dirty mice that have microbial exposure to improve preclinical models of human immune status and disease
The National Institute of Allergy and Infectious Diseases (NIAID) hosted a two-day virtual workshop on leveraging microbial exposure to improve mouse models of human immune status and disease. The workshop’s objective was to evaluate the current state of knowledge in the field and to identify gaps, challenges and future directions.
- Qian Liu
- , Thames Pickett
- & Barbara Rehermann
-
-
Research Briefing |
Human SHARPIN deficiency is linked to inborn errors of cell death
We report two patients with biallelic SHARPIN deficiency, which manifests with autoinflammation and B cell immunodeficiency and is phenotypically distinct from Sharpin deficiency in mice. In one patient, there was a significant shift from pro-survival signaling to cell-death signaling in fibroblasts and lymphoblasts induced by members of the TNF cytokine superfamily, accounting for the autoinflammation and immunodeficiency. Targeted therapy with TNF inhibitors had a dramatic beneficial effect.
-
Article |
Sepsis-trained macrophages promote antitumoral tissue-resident T cells
Here the authors show that sepsis and its resolution alter cancer susceptibility by epigenetically altering resident macrophages resulting in retention of T cells that increase antitumoral immunity.
- Alexis Broquet
- , Victor Gourain
- & Antoine Roquilly
-
Letter
| Open Access
Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease
Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.
- Felicity Liew
- , Claudia Efstathiou
- & J. Eunice Zhang
-
Article |
MEF2C regulates NK cell effector functions through control of lipid metabolism
Here the authors identify the transcription factor MEF2C as essential for human NK cell function and viral immunity in mice and humans. This control is exerted via regulation of lipid metabolism, and deficiency in MEF2C can be overcome by oleic acid supplementation.
- Joey H. Li
- , Adalia Zhou
- & Timothy E. O’Sullivan
-
-
Review Article |
Prenatal and postnatal neuroimmune interactions in neurodevelopmental disorders
In this Review, Kim et al. provide an overview of the prenatal immune conditions that contribute to the development of neurodevelopmental disorders and the immunological signatures and disorders associated with neurodevelopmental disorders.
- Eunha Kim
- , Jun R. Huh
- & Gloria B. Choi
-
Article
| Open Access
Thioredoxin is a metabolic rheostat controlling regulatory B cells
Here the authors show a mechanism by which mitochondrial electron transport and ROS contribute to the differentiation and function of regulatory B cells in the context of systemic lupus erythematosus.
- Hannah F. Bradford
- , Thomas C. R. McDonnell
- & Claudia Mauri
-
Resource
| Open Access
An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors
In this Resource article, the authors integrate genomic, bioinformatic and flow cytometric data from human bone marrow to provide an atlas of hematopoietic progenitor cell states in health and disease.
- Xuan Zhang
- , Baobao Song
- & H. Leighton Grimes
-
Article |
A method for predicting drugs that can boost the efficacy of immune checkpoint blockade
Here the authors present a method they call CM-Drug for the identification of combination drugs that can boost the efficacy of immune checkpoint blockade therapy. They validate this method with melanoma and lung cancer models in mice and explore in further depth one hit from their screen, the thyrotropin-releasing hormone (TRH) analog taltirelin.
- Yun Xia
- , Xin Li
- & An-Yuan Guo
-
Article
| Open Access
Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination
Here the authors use three different mouse models to show that prior infection or mRNA vaccination can protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) independently of antibodies, highlighting the importance of T cell-derived interferon-γ (IFN-γ) in host defense and the need to consider this measure of protection in vaccination.
- Valeria Fumagalli
- , Micol Ravà
- & Matteo Iannacone
-
Article |
The receptor binding domain of SARS-CoV-2 Omicron subvariants targets Siglec-9 to decrease its immunogenicity by preventing macrophage phagocytosis
Zhang and colleagues found that Omicron RBD binding to Siglec-9 impaired phagocytosis and antigen presentation in macrophages, an effect abrogated by an F375S mutation in the spike protein of Omicron.
- Xin He
- , Xiantao Zhang
- & Hui Zhang
-
Article |
Lupus autoantibodies initiate neuroinflammation sustained by continuous HMGB1:RAGE signaling and reversed by increased LAIR-1 expression
Systemic lupus erythematosus is associated with neurological impairment. Here the authors show that exposure of hippocampal neurons to lupus autoantibodies in mice initiates a neuroinflammatory state sustained by continuous HMGB1:RAGE signaling that can be reversed with an ACE inhibitor.
- Kaitlin R. Carroll
- , Mark Mizrachi
- & Betty Diamond
-
Article
| Open Access
Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
Smith and colleagues find that a multivariate signature of unresolved inflammation and altered iron homeostasis detected beyond 2 weeks following acute COVID-19 onset was the strongest early differentiator of those who report long COVID symptoms at 3–10 months.
- Aimee L. Hanson
- , Matthew P. Mulè
- & Kenneth G. C. Smith
-
News & Views |
A repair pathway lost in multiple sclerosis provides a new drug opportunity
A study identifies an increase in the tissue-protective factor HB-EGF during the initial stage of multiple sclerosis (MS), which is actively turned off as the disease worsens.
- Lise Torp Jensen
- , Kathrine E. Attfield
- & Lars Fugger
-
Article
| Open Access
The astrocyte-produced growth factor HB-EGF limits autoimmune CNS pathology
Linnerbauer and colleagues find that HB-EGF produced by reactive astrocytes is protective during autoimmune neuroinflammation, but epigenetically suppressed during late stages.
- Mathias Linnerbauer
- , Lena Lößlein
- & Veit Rothhammer
-
Article |
CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis
Here the authors use positron emission tomography to visualize fibroblasts in patients with arthritis and combined with spatial transcriptomic data show that these cells undergo a phenotypic shift upon resolution of inflammation. A CD200+DKK3+ fibroblast subset promotes this resolution by inhibiting tumor necrosis factor and interleukin-17A.
- Simon Rauber
- , Hashem Mohammadian
- & Andreas Ramming
-
Article
| Open Access
Mucosal vaccine-induced cross-reactive CD8+ T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection
Here, the authors enhance their nasally delivered chimpanzee adenoviral-vectored SARS-CoV-2 vaccine with an Omicron-matched vaccine (ChAd-SARS-CoV-2-BA.5-S) that stimulates mucosal immunity in mice and hamsters and shows cross-reactive CD8+ memory T cell-driven protection against antigenically distant strains.
- Baoling Ying
- , Tamarand L. Darling
- & Michael S. Diamond
-
News & Views |
Mapping brain–immune interactions in ischemic stroke
The development of therapies for ischemic stroke requires a deep understanding of the immune response to injury. Analysis now defines immune cell origin, disease stage-specific responses, and the effects of age and sex after ischemic stroke.
- Danye Jiang
- & Louise McCullough
-
Article
| Open Access
Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells
Siliciano and colleagues describe the generation of bispecific antibodies that target the HIV-1 envelope protein (Env) on the surface of HIV-1-infected cells and the receptor CD16 on the surface of NK cells to induce the NK cell-mediated lysis of HIV-1-infected cells and reduce the viral reservoir.
- Nathan L. Board
- , Zhe Yuan
- & Robert F. Siliciano
-
-
Article
| Open Access
Lithium carbonate revitalizes tumor-reactive CD8+ T cells by shunting lactic acid into mitochondria
Here the authors show that lithium carbonate can revitalize tumor-reactive CD8+T cells by shunting cytosolic lactic acid into the mitochondria for oxidation, indicating that lithium ions might be applied as a cancer immunotherapy.
- Jingwei Ma
- , Liang Tang
- & Bo Huang
-
Article |
Breaking NGF–TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection
Here the authors show that immune cell exclusion and immunosuppression in the melanoma microenviromment are driven by nerve growth factor interactions with tropomyosin receptor kinase A on melanoma cells and that a tropomyosin receptor kinase inhibitor can sensitize these tumors to immune checkpoint blockade.
- Tao Yin
- , Guoping Wang
- & Qi-Jing Li
-
Article |
GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway
Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.
- Ann Y. Park
- , Michael Leney-Greene
- & Michael J. Lenardo
-
-
-
News & Views |
Interferon-γ sensing by epithelial cells tames gut inflammation
Epithelial cells, macrophages and T cells are linked in a previously unknown regulatory circuit. Sensing of interferon-γ triggers antigen presentation by colonic epithelial cells, enabling T cells to lower extracellular ATP levels and reduce inflammation.
- Oliver Pabst
- & Vuk Cerovic
-
Review Article |
The pathophysiology of sepsis and precision-medicine-based immunotherapy
In this Review, Netea and colleagues summarize the latest research that contributes to our understanding of the pathophysiology of sepsis, and how this contributes to a new treatment approach through personalized immunotherapy.
- Evangelos J. Giamarellos-Bourboulis
- , Anna C. Aschenbrenner
- & Mihai G. Netea
-
Resource |
Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8+ T cells in persons with previous COVID-19
Koelle and colleagues use an activation marker-dependent approach to determine the recruitment of TCR by three doses of mRNA vaccination in individuals previously infected with SARS-CoV-2.
- Emily S. Ford
- , Koshlan Mayer-Blackwell
- & David M. Koelle
-
Review Article |
Forks in the road for CAR T and CAR NK cell cancer therapies
Here the authors review CAR T cell engineering and immunotherapy for cancer and juxtapose state-of-the-art developments with CAR NK cells as part of our Cancer Immunology series of Reviews.
- Oula K. Dagher
- & Avery D. Posey Jr.
-
-
Article |
A discrete ‘early-responder’ stromal-cell subtype orchestrates immunocyte recruitment to injured tissue
Mathis and colleagues identify a subset of muscle mesenchymal stromal cells that coordinates tissue immune responses and drives regenerative mechanisms following muscle injury.
- Omar K. Yaghi
- , Bola S. Hanna
- & Diane Mathis
-
Article
| Open Access
SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells
Huot et al. show that interferon-γ (IFN-γ) regulates the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in bronchoalveolar macrophages from cynomolgus macaques up to 18 months postinfection.
- Nicolas Huot
- , Cyril Planchais
- & Michaela Müller-Trutwin
-
Article |
Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach
Einav and colleagues characterize peripheral immune blood cells from pediatric patients with severe natural dengue infections. Their findings suggest that disease progression is associated with an inflammatory phenotype accompanied by impaired interferon response, defective antigen presentation and regulation of effector lymphocyte responses.
- Luca Ghita
- , Zhiyuan Yao
- & Shirit Einav
-
Article |
Fungal microbiota sustains lasting immune activation of neutrophils and their progenitors in severe COVID-19
Iliev et al. report that increased Candida albicans accumulation in the mycobiota of patients with severe COVID-19 might be a contributing factor to the immunopathology of severe COVID-19 and have long-lasting effects on the hematopoietic stem cell compartment.
- Takato Kusakabe
- , Woan-Yu Lin
- & Iliyan D. Iliev
-
Research Briefing |
ERMAP activates phagocytosis in Kupffer cells to restrict liver metastases
Kupffer cells, hepatic resident macrophages, are the first line of defense against liver metastases by engulfing disseminated malignant cells. We found that ERMAP expressed on tumor cells binds to galectin-9 and dectin-2 on Kupffer cells to deliver pro-phagocytosis ‘eat me’ signals to Kupffer cells to restrict liver metastases.
-
Article |
The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity
Yuan and colleagues show that ERMAP expression on cancer cells delivers an ‘eat me’ signal to Kupffer cells by binding to Gal-9–dectin-2 on Kupffer cells and triggering phagocytosis.
- Jie Li
- , Xiao-gang Liu
- & Ji-hang Yuan
-
Article
| Open Access
Depletion of slow-cycling PDGFRα+ADAM12+ mesenchymal cells promotes antitumor immunity by restricting macrophage efferocytosis
Peduto and colleagues report a role for ADAM12+ mesenchymal stromal cells at the tumor margins and their interaction with immune cells to promote a permissive ‘protumor’ environment.
- Selene E. Di Carlo
- , Jerome Raffenne
- & Lucie Peduto
-
World View |
How immunology can help reverse the pertussis vaccine failure
Current acellular pertussis vaccines prevent disease but do not prevent nasal infection and transmission of Bordetella pertussis. However, immunology is helping to design new vaccines that induce sterilizing immunity.
- Kingston H. G. Mills
-
Meeting Report |
Better understanding CD8+ T cells in cancer and viral infections
The first conference on ‘Infection and Immunity’ was organized by the Institute for Basic Science and Korean Association of Immunologists and held in Daejeon, South Korea, from 12 to 14 July 2023. The conference focused on the biology of CD8+ T cells in the context of viral disease and cancer.
- Hoyoung Lee
- , Min Kyung Jung
- & Eui-Cheol Shin
-
Research Briefing |
Human regulatory T cells turn into cytotoxic ‘exTreg’ cells in atherosclerosis
That regulatory T cells can change their phenotypes has been shown in mouse models of atherosclerosis and other autoimmune diseases. We suspected that this phenomenon would also be true in humans. To test this hypothesis, we developed a strategy to identify human ‘exTreg’ cells and found that they express a cytotoxic transcriptome.
Stuart Schlossman (1935–2023)