Sterile production of interferons in the thymus affects T cell repertoire selection DOI
K. Maude Ashby, Matouš Vobořil, Oscar Camilo Salgado

et al.

Science Immunology, Journal Year: 2024, Volume and Issue: 9(97)

Published: July 26, 2024

Type I and III interferons (IFNs) are robustly induced during infections protect cells against viral infection. Both type IFNs also produced at low levels in the thymus steady state; however, their role T cell development immune tolerance is unclear. Here, we found that both were constitutively by a very small number of AIRE + murine thymic epithelial cells, independent microbial stimulation. Antigen-presenting highly responsive to IFNs, required for activation maturation 1 conventional dendritic macrophages, B cells. Loss IFN sensing led reduced regulatory selection, receptor (TCR) repertoire diversity, enhanced autoreactive responses self-antigens expressed peripheral signaling. Thus, constitutive exposure generating tolerant diverse TCR repertoire.

Language: Английский

Microbiome and cancer DOI Creative Commons
Nyssa Cullin, Camila Azevedo Antunes, Ravid Straussman

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(10), P. 1317 - 1341

Published: Sept. 9, 2021

Language: Английский

Citations

370
The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis DOI Creative Commons
Saskia F. Erttmann,

Patrycja Swacha,

Kyaw Min Aung

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(5), P. 847 - 861.e10

Published: May 1, 2022

The microbiota are vital for immune homeostasis and provide a competitive barrier to bacterial fungal pathogens. Here, we investigated how gut commensals modulate systemic immunity response viral infection. Antibiotic suppression of the reduced tonic type I interferon (IFN-I) antiviral priming. microbiota-driven IFN-I-response was dependent on cGAS-STING but not TLR signaling or direct host-bacteria interactions. Instead, membrane vesicles (MVs) from extracellular bacteria activated cGAS-STING-IFN-I axis by delivering DNA into distal host cells. DNA-containing MVs were found in circulation promoted clearance both (herpes simplex virus 1) RNA (vesicular stomatitis virus) viruses cGAS-dependent manner. In summary, this study establishes an important role peripheral activation, which promotes resistance infections. Moreover, it uncovers underappreciated risk antibiotic use during

Language: Английский

Citations

219
Role of the cGAS–STING pathway in systemic and organ-specific diseases DOI Open Access
Sladjana Skopelja‐Gardner, Jie An, Keith B. Elkon

et al.

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(9), P. 558 - 572

Published: June 22, 2022

Language: Английский

Citations

174
Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides DOI Creative Commons
Yue Zheng, Rachelle L. Hunt,

Amer E. Villaruz

et al.

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(3), P. 301 - 313.e9

Published: Feb. 4, 2022

Language: Английский

Citations

161
Induction of mouse totipotent stem cells by a defined chemical cocktail DOI
Yanyan Hu, Yuanyuan Yang, Pengcheng Tan

et al.

Nature, Journal Year: 2022, Volume and Issue: 617(7962), P. 792 - 797

Published: June 21, 2022

Language: Английский

Citations

72
Skin immunity: dissecting the complex biology of our body's outer barrier DOI Creative Commons
Chenlu Zhang, Geil R. Merana, Tamia Harris-Tryon

et al.

Mucosal Immunology, Journal Year: 2022, Volume and Issue: 15(4), P. 551 - 561

Published: March 31, 2022

Our skin contributes critically to health via its role as a barrier tissue, carefully regulating passage of key substrates while also providing defense against exogenous threats. Immunological processes are integral almost every function and paramount our ability live symbiotically with commensal microbes other environmental stimuli. While many parallels can be drawn immunobiology at mucosal sites, immunity demonstrates unique features that relate distinct topography, chemical composition microbial ecology. Here we provide an overview immune organ, reference the broader context immunology. We review paradigms innate well adaptive highlight how skin-specific structures such hair follicles sebaceous glands interact contribute these processes. Finally, for immunology community few emerging areas interest field moving forward.

Language: Английский

Citations

70
Activation of human endogenous retroviruses and its physiological consequences DOI
Nicholas Dopkins, Douglas F. Nixon

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 212 - 222

Published: Oct. 23, 2023

Language: Английский

Citations

57
Conditioning of the immune system by the microbiome DOI Creative Commons
Daniel B. Graham, Ramnik J. Xavier

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(7), P. 499 - 511

Published: May 24, 2023

The human intestinal microbiome has coevolved with its host to establish a stable homeostatic relationship hallmark features of mutualistic symbioses, yet the mechanistic underpinnings host-microbiome interactions are incompletely understood. Thus, it is an opportune time conceive common framework for microbiome-mediated regulation immune function. We propose term conditioned immunity describe multifaceted mechanisms by which modulates immunity. In this regard, microbial colonization conditioning exposure that durable effects on function through action secondary metabolites, foreign molecular patterns, and antigens. Here, we discuss how spatial niches impact products at level dose timing, elicit diverse responses.

Language: Английский

Citations

50
Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans DOI Creative Commons
Verena M. Link, Poorani Subramanian,

Foo Cheung

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(2), P. 560 - 572

Published: Jan. 30, 2024

Abstract Nutrition has broad impacts on all physiological processes. However, how nutrition affects human immunity remains largely unknown. Here we explored the impact of a dietary intervention both and microbiota by performing post hoc analysis clinical trial in which each 20 participants sequentially consumed vegan or ketogenic diets for 2 weeks ( NCT03878108 ). Using multiomics approach including multidimensional flow cytometry, transcriptomic, proteomic, metabolomic metagenomic datasets, assessed diet, switch, host microbiota. Our data revealed that overall, diet was associated with significant upregulation pathways enrichment cells adaptive immune system. In contrast, had innate system, antiviral immunity. Both significantly differentially impacted microbiome host-associated amino acid metabolism, strong downregulation most microbial following compared baseline diet. Despite diversity participants, also observed tightly connected network between datasets driven compounds acids, lipids Collectively, this work demonstrates diverse controlled is sufficient to divergently immunity, could have implications precision nutritional interventions. ClinicalTrials.gov registration: .

Language: Английский

Citations

44
Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis DOI
Liang Chi, Can Liu, Inta Gribonika

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6692)

Published: April 4, 2024

Males and females exhibit profound differences in immune responses disease susceptibility. However, the factors responsible for sex tissue immunity remain poorly understood. Here, we uncovered a dominant role type 2 innate lymphoid cells (ILC2s) shaping sexual dimorphism within skin. Mechanistically, negative regulation of ILC2s by androgens leads to reduction dendritic cell accumulation activation males, along with reduced immunity. Collectively, our results reveal androgen-ILC2-dendritic axis controlling dimorphism. Moreover, this work proposes that set points are defined dual action hormones microbiota, strength local microbiota calibrating its tone.

Language: Английский

Citations

35