ArticleProceedings of the National Academy of Sciences of the United States of America2014
Commensal microbes drive intestinal inflammation by IL-17-producing CD4+ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- T cell receptor activation contributes to brain damage after intracerebral hemorrhage in mice.Journal of neuroinflammation · 2025Article
- Human IL-17A protein production is controlled through a PIP5K1α-dependent translational checkpoint.Science signaling · 2023Article
- Induction of T-helper-17-cell-mediated anti-tumour immunity by pathogen-mimicking polymer nanoparticles.Nature biomedical engineering · 2023Article
- "Molding" immunity-modulation of mucosal and systemic immunity by the intestinal mycobiome in health and disease.Mucosal immunology · 2022Review
- OX40L-OX40 Signaling in Atopic Dermatitis.Journal of clinical medicine · 2021Article
- Unregulated antigen-presenting cell activation by T cells breaks self tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The mammalian mycobiome: A complex system in a dynamic relationship with the host.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- From Discrete to Continuous Modeling of Lymphocyte Development and Plasticity in Chronic Diseases.Frontiers in immunology · 2019Review
- Ubc9 overexpression and SUMO1 deficiency blunt inflammation after intestinal ischemia/reperfusion.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- IL-23 and IL-1β Drive Human Th17 Cell Differentiation and Metabolic Reprogramming in Absence of CD28 Costimulation.Cell reports · 2018Article
- Equal Expansion of Endogenous Transplant-Specific Regulatory T Cell and Recruitment Into the Allograft During Rejection and Tolerance.Frontiers in immunology · 2018Article
- Commensal Fungi Recapitulate the Protective Benefits of Intestinal Bacteria.Cell host & microbe · 2017Article
- Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework.Infection and immunity · 2016Review
- The Costimulatory Receptor OX40 Inhibits Interleukin-17 Expression through Activation of Repressive Chromatin Remodeling Pathways.Immunity · 2016Article
- Macrophage polarization in response to oral commensals and pathogens.Pathogens and disease · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The costimulatory B7-1 (CD80)/B7-2 (CD86) molecules, along with T-cell receptor stimulation, together facilitate T-cell activation. This explains why in vivo B7 costimulation neutralization efficiently silences a variety of human autoimmune disorders. Paradoxically, however, B7 blockade also potently moderates accumulation of immune-suppressive regulatory T cells (Tregs) essential for protection against multiorgan systemic autoimmunity. Here we show that B7 deprivation in mice overrides the necessity for Tregs in averting systemic autoimmunity and inflammation in extraintestinal tissues, whereas peripherally induced Tregs retained in the absence of B7 selectively mitigate intestinal inflammation caused by Th17 effector CD4(+) T cells. The need for additional immune suppression in the intestine reflects commensal microbe-driven T-cell activation through the accessory costimulation molecules ICOSL and OX40L. Eradication of commensal enteric bacteria mitigates intestinal inflammation and IL-17 production triggered by Treg depletion in B7-deficient mice, whereas re-establishing intestinal colonization with Candida albicans primes expansion of Th17 cells with commensal specificity. Thus, neutralizing B7 costimulation uncovers an essential role for Tregs in selectively averting intestinal inflammation by Th17 CD4(+) T cells with commensal microbe specificity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.