Retinoic acid modulates peripheral blood helper innate lymphoid cell composition in vitro in patients with multiple sclerosis

This study investigates the frequency and numbers of circulating helper innate lymphoid cells (ILCs) in untreated relapsing-remitting multiple sclerosis (RRMS) patients, focusing on intracellular IL-10 and CCR6 expressions under IL-2, IL-33, and retinoic acid (RA) stimulation in vitro and their associations with clinical features in RRMS. In RRMS patients, ILC1 levels were notably higher upon IL-2 + IL-33 + RA stimulation, while ILC2 levels, particularly the c-Kit+ ILC2 and CCR6+ ILC2 subsets, were significantly lower compared to unstimulated conditions. Additionally, IL-10+ ILC1 levels were elevated. The ratios of IL-10+ ILC1/ILC1, c-Kit+ ILC2/c-Kit− ILC2, and CCR6+ ILC2/ILC2 were associated with the progression index (PI) in RRMS patients. [Display omitted] •ILC2 failed to expand with IL-2 and IL-33 alone.•Retinoic acid + IL-2+ IL33 converted ILC2s to ILC1s, driving ILC1 increase and a sharp reduction in c-Kit positive ILC2.•IL-10+ ILC1s were higher following retinoic acid, IL-2, and IL-33 stimulation.•CCR6+ ILC2 levels were dropped in IL-2 + IL-33 + retinoic acid.