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Updated: Apr 6, 2026

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A destructive feedback loop mediated by CXCL10 in central nervous system inflammatory disease

Wendy K Roberts1, Nathalie E Blachère1,2, Mayu O Frank1

  • 1Laboratory of Molecular Neuro-oncology, Rockefeller University, New York, NY.

Annals of Neurology
|July 31, 2015
PubMed
Abstract

Insights

Treatment with FK506 (tacrolimus) reduced CXCL10 levels in the cerebrospinal fluid (CSF) of paraneoplastic neurologic disorder (PND) patients. This suggests targeting T cells or CXCL10 may help interrupt CNS inflammation.

Area of Science:

  • Neuroimmunology
  • Oncology
  • Immunology

Background:

  • Paraneoplastic neurologic disorders (PND) are autoimmune conditions linked to cancer.
  • PND patients exhibit high-titer antibodies and T cells targeting tumor antigens.
  • FK506 (tacrolimus) is an immunosuppressant known to reduce CSF white blood cell counts in PND.

Purpose of the Study:

  • To investigate the impact of FK506 on cerebrospinal fluid (CSF) chemokine levels in PND patients.
  • To understand the role of CXCL10 in PND pathogenesis.

Main Methods:

  • Analyzed CSF samples from PND patients before and after FK506 treatment using a multiplex assay for 27 cytokines.
  • Conducted in vitro experiments to assess T cell secretion of CXCL10 in response to cognate antigen.

Main Results:

  • PND patients showed elevated levels of the chemokine CXCL10 in their CSF.
  • FK506 treatment significantly decreased CSF CXCL10 levels among the 27 cytokines tested.
  • In vitro, CXCL10 production by T cells required antigen-specific interactions and interferon-γ (IFNγ) receptor presence.

Conclusions:

  • Results support a model where PND antigen-specific T cell activation leads to IFNγ production, followed by CXCL10 secretion and lymphocyte recruitment.
  • Targeting T cells or CXCL10 in the central nervous system (CNS) may offer a therapeutic strategy to disrupt inflammatory feedback loops in PND.

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