Evidence map›Paper›PMID 28944315›Full record

ArticleCurrent opinion in toxicology2017

Is chronic AhR activation by rapidly metabolized ligands safe for the treatment of immune-mediated diseases?

Allison K Ehrlich, Nancy I Kerkvliet

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Current opinion in toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.0field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. Aryl Hydrocarbon Receptor Signalling in the Control of Gut Inflammation.International journal of molecular sciences · 2024
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. The absence of AhR in CD4Clinical epigenetics · 2022
    Article
  11. Review
  12. Review
  13. Review
  14. AHR in the intestinal microenvironment: safeguarding barrier function.Nature reviews. Gastroenterology & hepatology · 2021
    Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Allison K EhrlichDepartment of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331, United States.
Nancy I KerkvlietDepartment of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331, United States.
Oregon State University · US

Funding

MODE OF ACTION OF ENVIRONMENTAL TOXICANTST32ES007060 · NIEHS · OREGON STATE UNIVERSITY · PI Jamie DeWitt, Siva Kumar Kolluri · 1985 to 2026
$11.6M
The AHR as a Novel Pathway to the Induction of Regulatory T cellsR01ES016651 · NIEHS · OREGON STATE UNIVERSITY · PI KERKVLIET, NANCY I · 2009 to 2017
$3.5M
AhR activation and susceptibility to type 1 diabetesK99DK117509 · NIDDK · OREGON STATE UNIVERSITY · PI EHRLICH, ALLISON · 2017 to 2018
$182k
NIDDK NIH HHS K99 DK117509NIEHS NIH HHS R01 ES016651NIEHS NIH HHS T32 ES007060
6 · The paper itself

Abstract

There is a long standing perception that AhR ligands are automatically disqualified from pharmaceutical development due to their induction of Cyp1a1 as well as their potential for causing "dioxin-like" toxicities. However, recent discoveries of new AhR ligands with potential therapeutic applications have been reported, inviting reconsideration of this policy. One area of exploration is focused on the activation of AhR to promote the generation of regulatory T cells, which control the intensity and duration of immune responses. Rapidly metabolized AhR ligands (RMAhRLs), which do not bioaccumulate in the same manner as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) have been discovered that induce Tregs and display impressive therapeutic efficacy in a broad range of preclinical models of immune-mediated diseases. Given the promise of these RMAhRLs, is the bias against AhR activators still valid? Can RMAhRLs be given chronically to maintain therapeutic levels of AhR activation without producing the same toxicity profile as dioxin-like compounds? Based on our review of the data, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines. We also found no evidence that short-term treatment with RMAhRLs produce "dioxin-like toxicity" and, in fact, were well tolerated. However, safety testing of individual RMAhRLs under therapeutic conditions, as performed with all promising new drugs, will be needed to reveal whether or not chronic activation of AhR leads to unacceptable adverse outcomes.

Indexed as

AhR ligandsaryl hydrocarbon receptorimmune-mediated diseasesimmunotherapyTregs

Identifiers

PMID28944315
PMCPMC5607744
OpenAlexW2584858336

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.