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A host–microbiota interactome reveals extensive transkingdom connectivity
A new technology for proteome-scale assessment of human exoproteome–microbiome interactions exposes an extensive network of transkingdom connectivity.
- Nicole D. Sonnert
- , Connor E. Rosen
- & Noah W. Palm
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Article
| Open Access
IL-10 constrains sphingolipid metabolism to limit inflammation
IL-10 exerts its anti-inflammatory activity in macrophages by increasing the expression of enzymes that promote fatty acid desaturation and downstream regulation of the transcription factor REL.
- Autumn G. York
- , Mathias H. Skadow
- & Richard A. Flavell
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Article
| Open Access
Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques
Intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 in rhesus macaques.
- Katherine McMahan
- , Frank Wegmann
- & Dan H. Barouch
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Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization
An inhalable, single-dose dry powder aerosol SARS-CoV-2 vaccine shows good storage stability, results in sustained antigen delivery to antigen-presenting cells in the lungs and induces a potent antiviral immune response.
- Tong Ye
- , Zhouguang Jiao
- & Wei Wei
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Prevention of respiratory virus transmission by resident memory CD8+ T cells
Experiments in a mouse model of natural parainfluenza virus transmission show that tissue-resident memory T cells in the respiratory tract have important interferon-γ-dependent roles in protection against and limiting the transmission of viral disease.
- Ida Uddbäck
- , Sarah E. Michalets
- & Jacob E. Kohlmeier
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Metabolic programs of T cell tissue residency empower tumour immunity
A study describes the metabolic adaptations supporting differentiation, survival and function of tissue-resident memory CD8+ T cells and how to leverage them to enhance immunity against pathogens and tumours.
- Miguel Reina-Campos
- , Maximilian Heeg
- & Ananda W. Goldrath
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Article
| Open Access
Endothelial sensing of AHR ligands regulates intestinal homeostasis
Single-cell transcriptomics and in vivo challenge models establish a key role for the aryl hydrocarbon receptor in regulating the function of enteric endothelial cells in response to environmental cues.
- Benjamin G. Wiggins
- , Yi-Fang Wang
- & Chris Schiering
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Article
| Open Access
Immune sensing of food allergens promotes avoidance behaviour
A study using mouse models of food allergy shows that allergic sensitization drives antigen-specific avoidance behaviour mediated by immunoglobulin E antibodies and mast cells.
- Esther B. Florsheim
- , Nathaniel D. Bachtel
- & Ruslan Medzhitov
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Article |
Gut microbial fatty acid isomerization modulates intraepithelial T cells
A diet–microorganism pathway involving conjugated linoleic acid, interleukin-18, intraepithelial lymphocytes and the transcription factor hepatocyte nuclear factor 4γ modulates the host mucosal immune system.
- Xinyang Song
- , Haohao Zhang
- & Dennis L. Kasper
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Article
| Open Access
Active eosinophils regulate host defence and immune responses in colitis
Single-cell transcriptomic profiling and functional assays are used to identify subpopulations of eosinophils that are present in the mouse gastrointestinal tract and provide insight into the role of these cells in inflammatory bowel diseases in humans.
- Alessandra Gurtner
- , Costanza Borrelli
- & Isabelle C. Arnold
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Article |
Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation
Dietary inulin fibre alters the composition and metabolism of gut microbiota, resulting in elevated levels of bile acids that subsequently trigger mucosal type 2 inflammation characterized by eosinophilia, with clinical implications for allergy and anti-helminth defence.
- Mohammad Arifuzzaman
- , Tae Hyung Won
- & David Artis
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Article |
Non-redundant functions of group 2 innate lymphoid cells
Specific deletion of group 2 innate lymphoid cells in mice shows these cells have roles in the recruitment of eosinophils and in mounting immune and epithelial type 2 responses.
- Katja J. Jarick
- , Patrycja M. Topczewska
- & Christoph S. N. Klose
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Article |
The γδ IEL effector API5 masks genetic susceptibility to Paneth cell death
Intraepithelial lymphocytes expressing γ and δ T cell receptor subunits protect Paneth cells from cell death caused by viral infection or Crohn's disease.
- Yu Matsuzawa-Ishimoto
- , Xiaomin Yao
- & Ken Cadwell
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A RORγt+ cell instructs gut microbiota-specific Treg cell differentiation
Induction of T regulatory cells by gut microbes is mediated by antigen-presenting RORγt+ cells, unlike that of T follicular helper and T helper 17 cells, which requires different cell types.
- Ranit Kedmi
- , Tariq A. Najar
- & Dan R. Littman
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Article
| Open Access
Identification of trypsin-degrading commensals in the large intestine
Colonization of trypsin-degrading commensal bacteria may contribute to the maintenance of intestinal homeostasis and protection against pathogen infection in humans and mice.
- Youxian Li
- , Eiichiro Watanabe
- & Kenya Honda
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ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut
ILC3s expressing MHC class II control the fate of inflammatory versus tolerogenic T cells that respond to the microbiota by selecting for antigen-specific RORγt+ Treg cells and against TH17 cells, establishing intestinal homoeostasis.
- Mengze Lyu
- , Hiroaki Suzuki
- & Gregory F. Sonnenberg
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Article
| Open Access
Novel antigen-presenting cell imparts Treg-dependent tolerance to gut microbiota
Single-cell transcriptomic and epigenetic analysis has enabled the identification of Thetis cells, a class of RORγt+ antigen-presenting cells with a key role in the differentiation of commensal microbiota-induced peripheral regulatory T cells.
- Blossom Akagbosu
- , Zakieh Tayyebi
- & Chrysothemis C. Brown
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Article |
ZBTB46 defines and regulates ILC3s that protect the intestine
A subset of group 3 innate lymphoid cells (ILC3s) expresses the transcription factor ZBTB46—which was previously thought to be restricted to conventional dendritic cells—and these ILC3s have a role in regulating intestinal health.
- Wenqing Zhou
- , Lei Zhou
- & Gregory F. Sonnenberg
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Immune tolerance of food is mediated by layers of CD4+ T cell dysfunction
Immune tolerance to food is mediated by CD4+ T cells forming subsets of T helper cells lacking the capacity to trigger gut pathology but able to produce regulatory T cells that may suppress it.
- Sung-Wook Hong
- , Peter D. Krueger
- & Marc K. Jenkins
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Article |
Caspase-7 activates ASM to repair gasdermin and perforin pores
Caspase-7 cleaves and activates acid sphingomyelinase (ASM), which promotes the repair of gasdermin pores and thereby delays pore-driven lysis to allow other processes such as extrusion or apoptosis to occur before cell death.
- Kengo Nozaki
- , Vivien I. Maltez
- & Edward A. Miao
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Article |
Immune regulation by fungal strain diversity in inflammatory bowel disease
Genetically diverse Candida albicans strains in patients with inflammatory bowel disease secrete a toxin and aggravate IL-1β-dependent intestinal inflammation.
- Xin V. Li
- , Irina Leonardi
- & Iliyan D. Iliev
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Host immunomodulatory lipids created by symbionts from dietary amino acids
The symbiotic gut bacterium Bacteroides fragilis produces unique α-galactosylceramides from host dietary branched-chain amino acids, which are presented as CD1d ligands and immunomodulate natural killer T cells.
- Sungwhan F. Oh
- , T. Praveena
- & Dennis L. Kasper
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Early-life inflammation primes a T helper 2 cell–fibroblast niche in skin
Time-limited skin inflammation in neonatal mice promotes a reciprocal interaction between type 2 helper T cells and fascial fibroblasts that regulates wound repair in later life.
- Ian C. Boothby
- , Maxime J. Kinet
- & Michael D. Rosenblum
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Parallelism of intestinal secretory IgA shapes functional microbial fitness
The functional role of intestinal secretory IgA for host–microbiota interactions is investigated, showing that intestinal bacterial exposure leads to selection of diverse plasma cells that secrete antigen-specific IgA, which predominantly targets bacterial membranes.
- Tim Rollenske
- , Sophie Burkhalter
- & Andrew J. Macpherson
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Review Article |
A multilayered immune system through the lens of unconventional T cells
This Review provides an overview of our current understanding of the unconventional T cell compartment and discusses the development and function of unconventional T cells from an evolutionary perspective.
- Toufic Mayassi
- , Luis B. Barreiro
- & Bana Jabri
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Adaptive immunity induces mutualism between commensal eukaryotes
Studies of mouse and human IgA responses against Candida albicans and other common fungal species show that host adaptive immunity selects for fungal effectors that promote commensalism and prevent intestinal disease.
- Kyla S. Ost
- , Teresa R. O’Meara
- & June L. Round
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Acetate differentially regulates IgA reactivity to commensal bacteria
Acetate—a major gut microbial metabolite—increases the production of IgA in the colon, alters the capacity of the IgA pool to bind to specific microorganisms and alters the localization of these bacteria within the colon.
- Tadashi Takeuchi
- , Eiji Miyauchi
- & Hiroshi Ohno
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Article |
Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants
An engineered IgM antibody administered intranasally in mice shows high prophylactic efficacy and therapeutic efficacy against SARS-CoV-2, and is also effective against multiple variants of concern that are resistant to IgG-based therapeutics.
- Zhiqiang Ku
- , Xuping Xie
- & Zhiqiang An
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Article |
Thymic development of gut-microbiota-specific T cells
In young mice, antigens from the gut microbiota are trafficked by CX3CR1+ dendritic cells from the gut to the thymus, where they induce the expansion of T cells that are specific to commensal microorganisms.
- Daniel F. Zegarra-Ruiz
- , Dasom V. Kim
- & Gretchen E. Diehl
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Article |
CAR directs T cell adaptation to bile acids in the small intestine
Activation of the nuclear hormone receptor CAR in T cells protects the small intestine against bile acid-driven inflammation.
- Mei Lan Chen
- , Xiangsheng Huang
- & Mark S. Sundrud
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Article |
Expansible residence decentralizes immune homeostasis
Investigations in mice using parabiosis and cohousing experiments reveal that nonlymphoid organs serve as reservoirs of tissue-autonomous cellular immunity, leading to the decentralization of organism-level immune homeostasis.
- Sathi Wijeyesinghe
- , Lalit K. Beura
- & David Masopust
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Article |
Mucosal or systemic microbiota exposures shape the B cell repertoire
A mouse model of systemic versus mucosal exposure to microbial taxa reveals that the former provokes a flexible B cell response with a diverse immunoglobulin repertoire, whereas the latter generates a more-restricted response.
- Hai Li
- , Julien P. Limenitakis
- & Andrew J. Macpherson
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Article |
The liver–brain–gut neural arc maintains the Treg cell niche in the gut
A liver–brain–gut neural circuit responds to the gut microenvironment and regulates the activity of peripheral regulatory T cells in the colon by controlling intestinal antigen-presenting cells in a muscarinic signalling-dependent manner.
- Toshiaki Teratani
- , Yohei Mikami
- & Takanori Kanai
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Article |
Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells
The secondary bile acid 3β-hydroxy-deoxycholic (isodeoxycholic) acid, produced by gut bacteria, promotes the generation of colonic extrathymic regulatory T cells, whose immunosuppressive activities are known to be essential for intestinal health.
- Clarissa Campbell
- , Peter T. McKenney
- & Alexander Y. Rudensky
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Article |
IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease
An HLA- and gluten-dependent mouse model of coeliac disease with villous atrophy provides evidence for the cooperative role of IL-15 and gluten-specific CD4+ T cells in licensing the full activation of cytotoxic T cells that are necessary for inducing epithelial damage.
- Valérie Abadie
- , Sangman M. Kim
- & Bana Jabri
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Article |
Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis
Both dietary and microbial factors influence the composition of the gut bile acid pool, which in turn modulates the frequencies and functionalities of RORγ-expressing colonic FOXP3+ regulatory T cells, contributing to protection from inflammatory colitis.
- Xinyang Song
- , Ximei Sun
- & Dennis L. Kasper
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Letter |
Light-entrained and brain-tuned circadian circuits regulate ILC3s and gut homeostasis
Circadian circuits, entrained by light and tuned by the brain, regulate intestinal group 3 innate lymphoid cells in mice, along with epithelial reactivity, microbiome composition and lipid metabolism.
- Cristina Godinho-Silva
- , Rita G. Domingues
- & Henrique Veiga-Fernandes
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Letter |
Compartmentalized gut lymph node drainage dictates adaptive immune responses
Immune responses in the gut and associated draining lymph nodes differ between tolerogenic and inflammatory depending on their anatomical location.
- Daria Esterházy
- , Maria C. C. Canesso
- & Daniel Mucida
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Letter |
Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2
A microbiota- and IL-1β-dependent axis of IL-2 production by group-3 innate lymphoid cells is shown in a mouse model to be necessary to maintain immunological homeostasis and regulatory T cells in the small intestine.
- Lei Zhou
- , Coco Chu
- & Gregory F. Sonnenberg
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Article |
A defined commensal consortium elicits CD8 T cells and anti-cancer immunity
A consortium of 11 bacterial strains from the healthy human gut microbiota can strongly induce interferon-γ-producing CD8 T cells in the intestine, and enhance both resistance to bacterial infection and the therapeutic efficacy of immune checkpoint inhibitors.
- Takeshi Tanoue
- , Satoru Morita
- & Kenya Honda
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Letter |
GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites
In the mouse intestine, pyruvate and lactate produced from bacterial metabolites enhance immune responses through inducing dendrite protrusion, mediated by GPR31, of small intestinal mononuclear cells that express CX3CR1.
- Naoki Morita
- , Eiji Umemoto
- & Kiyoshi Takeda
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Letter |
The translation of non-canonical open reading frames controls mucosal immunity
In mouse macrophages, a range of short and non-ATG-initiated open reading frames that can generate proteins are identified, one of which is shown to be essential for host immunity to enteric mucosal infection and inflammation.
- Ruaidhrí Jackson
- , Lina Kroehling
- & Richard A. Flavell
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Letter |
Allergic inflammatory memory in human respiratory epithelial progenitor cells
Single-cell RNA sequencing is used to characterize cell types in nasal tissues from human patients with chronic rhinosinusitis, revealing a role for tissue stem cells in allergic inflammatory memory.
- Jose Ordovas-Montanes
- , Daniel F. Dwyer
- & Alex K. Shalek
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Letter |
Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche
Larvae of the parasitic helminth Heligmosomoides polygyrus induce granuloma formation and a fetal-like developmental program in granuloma-associated crypts of infected adult mice.
- Ysbrand M. Nusse
- , Adam K. Savage
- & Ophir D. Klein
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Letter |
c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont
The transcription factor c-MAF is required for the generation of Helicobacter-specific regulatory T cells that selectively restrain pro-inflammatory TH17 cells; the absence of c-MAF in mouse regulatory T cells results in pathobiont-dependent inflammatory bowel disease.
- Mo Xu
- , Maria Pokrovskii
- & Dan R. Littman
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Letter |
Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism
Distinct populations of lymphocytes act sequentially during development to direct maturation of the mammalian gut microbiota.
- Kairui Mao
- , Antonio P. Baptista
- & Ronald N. Germain
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Letter |
Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring
Maternal immune activation (MIA)-mediated abnormal behavioural phenotypes require defined gut commensal bacteria for the induction of IL-17-producing T helper 17 cells.
- Sangdoo Kim
- , Hyunju Kim
- & Jun R. Huh
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Letter |
The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation
Intestinal type 2 innate lymphoid cells express the neuropeptide receptor NMUR1, which makes them responsive to neuronal neuromedin U, thereby promoting a type 2 cytokine response and accelerated expulsion of the gastro-intestinal nematode Nippostrongylus brasiliensis.
- Christoph S. N. Klose
- , Tanel Mahlakõiv
- & David Artis
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Letter |
High-avidity IgA protects the intestine by enchaining growing bacteria
Oral-vaccine-induced IgA cross-links growing bacteria into clonal aggregates, inhibiting pathogenesis, adaption and the spread of antimicrobial resistance genes.
- Kathrin Moor
- , Médéric Diard
- & Emma Slack
Immune microniches shape intestinal Treg function