Circulating CCR6+ILC proportions are lower in multiple sclerosis patients

Florentina Aglas-Leitner1,2, Pierre Juillard1, Anette Juillard1

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

Insights

Innate lymphoid cells (ILC) play a role in multiple sclerosis (MS). CD56bright natural killer (NK) cells expand during relapse, and altered helper ILC proportions suggest changes in central nervous system (CNS) migration in MS patients.

Area of Science:

  • Immunology
  • Neuroimmunology
  • Cellular Biology

Background:

  • The role of innate lymphoid cells (ILC), especially helper ILC, in the pathogenesis of multiple sclerosis (MS) remains unclear.
  • Understanding ILC dynamics in MS is crucial for developing targeted therapies.

Purpose of the Study:

  • To comprehensively analyze peripheral ILC subsets in MS patients before and after alemtuzumab treatment.
  • To investigate MS-related immunophenotypic shifts in ILC using mass cytometry and advanced computational analysis.

Main Methods:

  • Mass cytometry was employed to analyze circulating ILC subsets in MS patients and non-MS controls.
  • Alemtuzumab treatment effects were assessed by comparing ILC profiles pre- and post-administration.
  • Fast interpolation-based t-SNE (Flt-SNE) was used for dimensionality reduction to elucidate ILC immunophenotypic shifts.

Main Results:

  • Alemtuzumab treatment did not alter overall levels of natural killer (NK) cells or helper ILC (ILC1, ILC2, ILC3).
  • CD56bright NK cell expansions were observed in relapsing MS patients.
  • MS patients showed proportional shifts from ILC1 to ILC2 and decreased proportions of CCR6+ helper ILC prior to alemtuzumab treatment.

Conclusions:

  • CD56bright NK cell expansion during relapse suggests an immediate immune response to disease reactivation in MS.
  • CCR6-related shifts in helper ILC indicate potential alterations in their migration to the central nervous system (CNS) in MS patients.
Abstract