Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Cxcr3-expressing leukocytes are necessary for neurofibroma formation in mice
Jonathan S. Fletcher, … , Nathan Salomonis, Nancy Ratner
Jonathan S. Fletcher, … , Nathan Salomonis, Nancy Ratner
Published February 7, 2019
Citation Information: JCI Insight. 2019;4(3):e98601. https://doi.org/10.1172/jci.insight.98601.
View: Text | PDF
Research Article Inflammation Neuroscience

Cxcr3-expressing leukocytes are necessary for neurofibroma formation in mice

  • Text
  • PDF
Abstract

Plexiform neurofibroma is a major contributor to morbidity in patients with neurofibromatosis type I (NF1). Macrophages and mast cells infiltrate neurofibroma, and data from mouse models implicate these leukocytes in neurofibroma development. Antiinflammatory therapy targeting these cell populations has been suggested as a means to prevent neurofibroma development. Here, we compare gene expression in Nf1-mutant nerves, which invariably form neurofibroma, and show disruption of neuron–glial cell interactions and immune cell infiltration to mouse models, which rarely progresses to neurofibroma with or without disruption of neuron–glial cell interactions. We find that the chemokine Cxcl10 is uniquely upregulated in NF1 mice that invariably develop neurofibroma. Global deletion of the CXCL10 receptor Cxcr3 prevented neurofibroma development in these neurofibroma-prone mice, and an anti–Cxcr3 antibody somewhat reduced tumor numbers. Cxcr3 expression localized to T cells and DCs in both inflamed nerves and neurofibromas, and Cxcr3 expression was necessary to sustain elevated macrophage numbers in Nf1-mutant nerves. To our knowledge, these data support a heretofore-unappreciated role for T cells and DCs in neurofibroma initiation.

Authors

Jonathan S. Fletcher, Jianqiang Wu, Walter J. Jessen, Jay Pundavela, Jacob A. Miller, Eva Dombi, Mi-Ok Kim, Tilat A. Rizvi, Kashish Chetal, Nathan Salomonis, Nancy Ratner

×

Supplemental Table 1 - Download (33.99 KB)

No preview available for this file type
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts