Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Specialty Sites
    • COVID-19
    • Without Borders
    • Equity, Diversity, and Inclusion
    • Innovations in Care Delivery
    • Practice Current
  • Collections
    • Topics A-Z
    • Residents & Fellows
    • Infographics
    • Patient Pages
    • Null Hypothesis
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Specialty Sites
    • COVID-19
    • Without Borders
    • Equity, Diversity, and Inclusion
    • Innovations in Care Delivery
    • Practice Current
  • Collections
    • Topics A-Z
    • Residents & Fellows
    • Infographics
    • Patient Pages
    • Null Hypothesis
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Articles
  • Issues

User menu

  • My Alerts
  • Log in

Search

  • Advanced search
Neurology Neuroimmunology & Neuroinflammation
Home
A peer-reviewed clinical and translational neurology open access journal
  • My Alerts
  • Log in
Site Logo
  • Home
  • Articles
  • Issues

Share

March 2021; 8 (2) ArticleOpen Access

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

Veit Rothhammer, Jessica E. Kenison, View ORCID ProfileZahorong Li, Emily Tjon, Maisa C. Takenaka, Chun-Cheih Chao, View ORCID ProfileKalil Alves de Lima, Davis M. Borucki, Joel Kaye, View ORCID ProfileFrancisco J. Quintana
First published January 6, 2021, DOI: https://doi.org/10.1212/NXI.0000000000000946
Veit Rothhammer
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: veit.rothhammer@tum.de
Jessica E. Kenison
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jessica.kenison@antolrx.com
Zahorong Li
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Zahorong Li
  • For correspondence: zli37@bwh.harvard.edu
Emily Tjon
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: emilyctjon@gmail.com
Maisa C. Takenaka
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: mcstakenaka@gmail.com
Chun-Cheih Chao
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: u911636@gmail.com
Kalil Alves de Lima
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kalil Alves de Lima
  • For correspondence: kalil.delima@gmail.com
Davis M. Borucki
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: boruckid@musc.edu
Joel Kaye
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: joel.k@ayalapharma.com
Francisco J. Quintana
From 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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Francisco J. Quintana
Full PDF
Citation
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
Neurol Neuroimmunol Neuroinflamm Mar 2021, 8 (2) e946; DOI: 10.1212/NXI.0000000000000946

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
260

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

Objective MS 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.

Methods We 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.

Results We 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.

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

Glossary

AHR=
aryl hydrocarbon receptor;
EAE=
experimental autoimmune encephalomyelitis;
EDTA=
ethylenediaminetetraacetic acid;
GFAP=
glial fibrillary acidic protein;
GSEA=
gene set enrichment analyses;
IL=
interleukin;
IPA=
ingenuity pathway analysis;
Laq=
laquinimod;
NF-κB=
nuclear factor kappa B;
PPMS=
primary progressive MS;
qPCR=
quantitative PCR;
RRMS=
relapsing-remitting MS;
SPMS=
secondary progressive MS;
TNFα=
tumor necrosis factor-α

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • The Article Processing Charge was funded by the NIH.

  • Received June 12, 2020.
  • Accepted in final form November 4, 2020.
  • Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

View Full Text

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

NOTE: All contributors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.nn.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.

  • Stay timely. Submit only on articles published within the last 8 weeks.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • 200 words maximum.
  • 5 references maximum. Reference 1 must be the article on which you are commenting.
  • 5 authors maximum. Exception: replies can include all original authors of the article.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Letters

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Letters Submission Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Glossary
    • Methods
    • Results
    • Discussion
    • Study Funding
    • Disclosure
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures

Related Articles

  • No related articles found.

Topics Discussed

  • Multiple sclerosis

Alert Me

  • Alert me when eletters are published
Advertisement
Neurology - Neuroimmunology Neuroinflammation: 8 (4)

Articles

  • Articles
  • Issues
  • Popular Articles

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2021 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise