Evidence map›Paper›PMID 33408169›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2021

Aryl Hydrocarbon Receptor Activation in Astrocytes by Laquinimod Ameliorates Autoimmune Inflammation in the CNS.

Veit Rothhammer, Jessica E Kenison, Zahorong Li, Emily Tjon, Maisa C Takenaka, Chun-Cheih Chao, Kalil Alves de Lima, Davis M Borucki, Joel Kaye, Francisco J Quintana

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

Article in Neurology(R) neuroimmunology & neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

33 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
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

10 authors at 1 institution in 2 countries.

Veit RothhammerFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA.
Jessica E KenisonFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA.
Zahorong LiFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA.ORCID 0000-0002-5268-6986
Emily TjonFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA.
Maisa C TakenakaFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA.
Chun-Cheih ChaoFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA.
Kalil Alves de LimaFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA.ORCID 0000-0002-9149-168X
Davis M BoruckiFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA.
Joel KayeFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA.
Francisco J QuintanaFrom the Ann Romney Center for Neurologic Diseases (V.R., J.E.K., Z.L., E.T., M.C.T., C.-C.C., K.A.d.L., D.M.B., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Klinikum rechts der Isar (V.R.), Department of Neurology, Technical University of Munich, Germany; Department of Neurology (V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany; Ayala Pharmaceuticals (J.K.), Rehovot, Israel; and Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA. fquintana@rics.bwh.harvard.edu.ORCID 0000-0001-8156-0736
Broad Institute · US

Funding

Control of Local CNS InflammationR01NS102807 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI QUINTANA, FRANCISCO J. · 2018 to 2022
$1.8M
NINDS NIH HHS R01 NS102807
6 · The paper itself

Abstract

objectiveMS is an autoimmune demyelinating disease of the CNS, which causes neurologic deficits in young adults and leads to progressive disability. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, can drive anti-inflammatory functions in peripheral immune cells and also in CNS-resident cells. Laquinimod is a drug developed for the treatment of MS known to activate AHR, but the cellular targets of laquinimod are still not completely known. In this work, we analyzed the contribution of AHR activation in astrocytes to its beneficial effects in the experimental autoimmune encephalomyelitis (EAE) preclinical model of MS.

methodsWe used conditional knockout mice, in combination with genome-wide analysis of gene expression by RNA-seq and in vitro culture systems to investigate the effects of laquinimod on astrocytes.

resultsWe found that AHR activation in astrocytes by laquinimod ameliorates EAE, a preclinical model of MS. Genome-wide RNA-seq transcriptional analyses detected anti-inflammatory effects of laquinimod in glial cells during EAE. Moreover, we established that the Delaq metabolite of laquinimod dampens proinflammatory mediator production while activating tissue-protective mechanisms in glia.

conclusionsTaken together, these findings suggest that AHR activation by clinically relevant AHR agonists may represent a novel therapeutic approach for the treatment of MS.

Indexed as

AnimalsAstrocytesBasic Helix-Loop-Helix ProteinsEncephalomyelitis, Autoimmune, ExperimentalFemaleMiceMice, Inbred C57BLMice, KnockoutQuinolonesReceptors, Aryl HydrocarbonAhr protein, mouseBasic Helix-Loop-Helix ProteinslaquinimodQuinolonesReceptors, Aryl Hydrocarbon

Identifiers

PMID33408169
PMCPMC7862099
OpenAlexW3119709081

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.