RORγt eTACs mediate oral tolerance and Treg induction

The Journal of Experimental Medicine, Journal Year: 2025, Volume and Issue: 222(8)

Published: April 15, 2025

The immune system must distinguish pathogens from innocuous dietary antigens, but the precise mechanisms and cellular actors remain unclear. Here, we demonstrate that RORγt-lineage APCs are required for oral tolerance. Using lineage tracing single-cell sequencing, show these consist of three principal populations: type 3 innate lymphoid cells (ILC3s), dendritic cells, expressing Aire called RORγt eTACs (R-eTACs)-also known as Janus or Thetis cells. We R-eTACs, not ILC3s, tolerance induction. find R-eTACs probable myeloid origin uniquely express integrin β8 (Itgb8). Both MHCII Itgb8 expression in necessary to induce food-specific regulatory T Mice lacking with deletion fail generate Tregs instead develop a T-follicular helper response elevated antigen-specific antibodies. These findings establish critical mediators suggest novel targets modulate

Language: Английский

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2′-FL in Dairy Matrices Attenuates Allergic Symptoms in Mice by Reducing BLG Hypersensitivity and Modulating Gut Microecology

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

2'-Fucosyllactose (2'-FL), an industrial breast milk oligosaccharide, is approved for use in infant formula and may reduce cow's protein allergenicity. To investigate whether glycosylation products of 2'-FL dairy (2'-FL-β-LG) increase its sensitization, we cross-linked β-LG with used it to sensitize Balb/c mice, comparing nonglycosylated β-LG. Both 2'-FL-β-LG sensitization oral intervention reduced allergic symptoms, specific antibodies (IgE, IgG, IgG2a), inflammatory cytokine levels, intestinal damage. also shifted T-cell differentiation, cell surface expression DC receptors, enhanced gut microbial diversity. Oral showed the greatest efficacy, suggesting potential lowering allergenicity formula.

Language: Английский

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A wave of Thetis cells imparts tolerance to food antigens early in life

Science, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

Within the intestine, peripherally-induced regulatory T (pTreg) cells play an essential role in suppressing inflammatory responses to food proteins. However, identity of antigen-presenting (APC) that instruct food-specific pTreg is poorly understood. Here, we found a subset Thetis cells, TC IV, required for cell differentiation. IV were almost exclusively present within mesenteric lymph nodes suggesting presence underlies phenomenon oral tolerance. A wave differentiation peri-weaning period was associated with window opportunity enhanced generation response antigens. Our findings indicate may represent therapeutic target treatment food-associated allergic and diseases.

Language: Английский

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There’s no place like home: How local tissue microenvironments shape the function of innate lymphoid cells

Mucosal Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Innate lymphoid cells (ILC) have emerged as critical immune effectors with key roles in orchestrating the wider response. While ILC are relatively rare they found enriched within discrete microenvironments, predominantly barrier tissues. An emerging body of evidence implicates complex and multi-layered interactions between cell types, tissue structure external environment determinants function these niches. In this review we will discuss specific components that constitute ILC-associated microenvironments consider how act to determine health disease. The development holistic, integrated models environments inform new understanding contextual cues mechanisms protective versus disease-causing family.

Language: Английский

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Probiotic Lactobacillus johnsonii Reduces Intestinal Inflammation and Rebalances Splenic Treg/Th17 Responses in Dextran Sulfate Sodium-Induced Colitis

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 433 - 433

Published: April 3, 2025

Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gastrointestinal tract, is frequently complicated by extraintestinal manifestations such as functional hyposplenism. Increasing evidence highlights its pathogenesis multifactorial interplay gut dysbiosis, intestinal barrier dysfunction, and dysregulated immune responses. While probiotics, particularly Lactobacillus spp., have emerged potential therapeutics for IBD, restoring homeostasis, their systemic immunomodulatory effects remain underexplored. Here, we investigated protective role johnsonii N5 in DSS-induced colitis, focusing on inflammation inhibition splenic T cell regulation. Pretreatment with L. significantly attenuated colitis severity, evidenced preserved body weight, reduced activity index, prevention colon shortening. suppressed colonic pro-inflammatory factors TNF-α, Il-1b, Il-6, CXCL1, while elevating anti-inflammatory IL-10 at both mRNA protein levels. Transcriptomic analysis spleen revealed that mediated downregulation pathways, including IL-17 TNF signaling well HIF-1 pathway, modulated metabolic pathway oxidative phosphorylation. Flow cytometry demonstrated rebalanced Treg/Th17 responses expanding Treg population reducing production IL-17A Th17 cells. Notably, Th17-associated positively correlated mediators, emphasizing cells driving colitis. In contrast, abundance levels, suggesting link between regulation Our study underscores therapeutic targeting gut–immune crosstalk through thereby offering valuable insights developing live bacterial-based interventions IBD other disorders.

Language: Английский

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Tolerance requires diversity (of antigen presenting cells)

Science Immunology, Journal Year: 2025, Volume and Issue: 10(107)

Published: May 2, 2025

Multiple APC subsets cooperate to induce regulatory T cells in the gut.

Language: Английский

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Parasite and host immune factors that impact the development of a mucosal vaccine for Cryptosporidium

Mucosal Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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Thetis cells: regulators of intestinal immune tolerance

Current Opinion in Immunology, Journal Year: 2025, Volume and Issue: 95, P. 102570 - 102570

Published: May 26, 2025

Language: Английский

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RORγt+ antigen-presenting cells mediate food tolerance

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 29, 2025

Language: Английский

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