Circulating CCR6+ILC proportions are lower in multiple sclerosis patients

Florentina Aglas-Leitner; Pierre Juillard; Anette Juillard; Scott N Byrne; Simon Hawke; Georges E Grau; Felix Marsh-Wakefield

doi:10.1002/cti2.1426

Circulating CCR6⁺ILC proportions are lower in multiple sclerosis patients

Clin Transl Immunology. 2022 Dec 23;11(12):e1426. doi: 10.1002/cti2.1426. eCollection 2022.

Authors

Florentina Aglas-Leitner^{1

2}, Pierre Juillard¹, Anette Juillard¹, Scott N Byrne^{3

4}, Simon Hawke^{1

5}, Georges E Grau¹, Felix Marsh-Wakefield^{1

6

7}

Affiliations

¹ Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health The University of Sydney Sydney NSW Australia.
² Medical University of Vienna Vienna Austria.
³ Centre for Immunology and Allergy Research The Westmead Institute for Medical Research Sydney NSW Australia.
⁴ Faculty of Medicine and Health, School of Medical Sciences The University of Sydney Sydney NSW Australia.
⁵ Central West Neurology and Neurosurgery Orange NSW Australia.
⁶ Liver Injury & Cancer Program Centenary Institute Sydney NSW Australia.
⁷ Human Cancer & Viral Immunology Laboratory The University of Sydney Sydney NSW Australia.

Abstract

Objectives: The role of innate lymphoid cells (ILC), particularly helper ILC, in the pathogenesis of multiple sclerosis (MS) is not well understood. Here, we present a comprehensive analysis of peripheral ILC subsets in MS patients prior and after alemtuzumab administration using mass cytometry.

Methods: Circulating ILC were analysed by mass cytometry in MS patients before and after alemtuzumab. These were compared with non-MS controls. MS-related shifts among ILC immunophenotypes were further elucidated by fast interpolation-based t-SNE (Flt-SNE) dimensionality reduction.

Results: Neither natural killer (NK) cells nor helper ILC (ILC1, ILC2 and ILC3) levels were altered following alemtuzumab treatment. However, CD56^bright NK cell expansions were observed in relapsing patients. MS patients prior to alemtuzumab further displayed proportional shifts from ILC1 to ILC2, with MS-associated decreases in CCR6⁺ helper ILC proportions.

Conclusion: CD56^bright NK cells during relapse indicate an immediate response to disease reactivation, while CCR6-related shifts among helper ILC suggest altered ILC migration to the CNS during MS.

Keywords: CCR6; ILC; MS; NK cells; alemtuzumab.