Scott Byrne

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.