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Mass cytometry reveals cladribine-induced resets among innate lymphoid cells in multiple sclerosis

F T Aglas-Leitner1,2, P Juillard1, A Juillard1

  • 1Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Scientific Reports
|November 27, 2022
PubMed

Insights

Cladribine tablets (CladT) reduce most innate lymphoid cell (ILC) subsets in relapsing/remitting multiple sclerosis (RRMS) patients. However, specific ILC subsets and NK cells are spared, suggesting immune system reconstitution towards tolerance.

Area of Science:

  • Immunology
  • Neuroimmunology
  • Cell Biology

Background:

  • Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
  • Innate lymphoid cells (ILCs) play a role in immune regulation and inflammation.
  • Understanding the impact of immunomodulatory therapies on ILCs is crucial for MS treatment.

Purpose of the Study:

  • To comprehensively analyze peripheral innate lymphoid cell (ILC) subsets in relapsing/remitting MS (RRMS) patients before and after cladribine tablets (CladT) treatment.
  • To investigate the specific effects of CladT on different ILC subsets, including NK cells.

Main Methods:

  • Mass cytometry (CyTOF) analysis of peripheral blood mononuclear cells (PBMCs) from RRMS patients and healthy controls.
  • Dimensionality reduction techniques for immunophenotyping ILC subsets.
  • Longitudinal analysis at baseline, 2 months, and 6 months post-CladT initiation.

Main Results:

  • CladT significantly reduced most ILC subsets, except for CD56bright NK cells and ILC2.
  • CD38+ NK cells and CCR6+ ILC3 subsets were notably excluded from CladT-induced reductions.
  • Post-treatment analysis revealed increased CD5+ ILC1 proportions at 2 months and boosted CD38-CD56bright NK cell numbers at 6 months, indicating ILC reconstitution.

Conclusions:

  • CladT induces immune cell depletion among ILCs but spares specific subsets like CD56bright NK cells and ILC2.
  • The observed post-treatment ILC expansions suggest a reconstitution of the immune system towards a more tolerant phenotype in RRMS patients.
  • These findings provide insights into the immunomodulatory effects of CladT on ILCs in MS.

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