Enteropathy-induced regulatory T cells inhibit intestinal CD4+ T cell responses against oral vaccines
Bhattacharjee, A.; Burr, A. H. P.; Overacre-Delgoffe, A. E.; Tometich, J. T.; Yang, D.; Huckestein, B. R.; Linehan, J. L.; Spencer, S. P.; Hall, J. A.; Harrison, O. J.; Morais da Fonseca, D.; Norton, E. B.; Belkaid, Y.; Hand, T. W.
Show abstract
Environmental Enteric Dysfunction (EED) is an intestinal disease caused by malnutrition and infection that leads to malabsorption and stunting. EED is also associated with a reduced efficacy of oral vaccines. We show in a microbiota and diet-dependent model of EED that oral vaccine-specific CD4+ T cell responses fail in the small intestine but responses in the draining lymph node were unaffected. Accordingly, the number of immunosuppressive ROR{gamma}T+FOXP3+ Tregs in the small intestine inversely correlated with the response to oral vaccination. Depletion of ROR{gamma}T+FOXP3+ Tregs indicated that they were necessary for EED-associated inhibition of the vaccine response. Additionally, ROR{gamma}T+FOXP3+ Tregs are important to regulate EED-associated inflammation as their depletion significantly worsened stunting. We have shown that EED-associated intestinal inflammation leads to a localized intestinal blockade of CD4 T cell immunity. These results support a modular model for immunity where tissue responses can be regulated independently of systemic immunity to prevent autoinflammation.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Macrophages regulate gastrointestinal motility through complement component 1q 96%
- Pyroptosis-dependent and -independent cross-priming of CD8+ T cells by intestinal epithelial cell-derived antigen 96%
- Homeostatic activation of Aryl Hydrocarbon Receptor by dietary ligands dampens cutaneous allergic responses by controlling Langerhans cells migration 94%
Similar papers in this journal
- Mucolytic bacteria license pathobionts to acquire host-derived nutrients during dietary nutrient restriction 96%
- Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes 96%
- Lysophosphatidic acid-mediated GPR35 signaling in CX3CR1+ macrophages regulates the intestinal cytokine milieu 96%
Similar papers in this journal
- Sustained post-developmental T-bet expression is critical for the maintenance of type 1 innate lymphoid cells in vivo 95%
- Multiple environmental signaling pathways control the differentiation of RORγt-expressing regulatory T cells 94%
- Selective ablation of thymic and peripheral Foxp3+ regulatory T cell development 94%
Similar papers in this journal
- IL-10 inhibits STAT1-dependent macrophage accumulation during microbiota-induced colitis 95%
- A transmissible γδ intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection. 94%
- Liver X Receptor regulates Th17 and RORγt+ Treg cells by distinct mechanisms 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.