Neuromyelitis optica spectrum disorder (NMOSD) is a severe central nervous system (CNS) autoimmune disease that primarily damages the optic nerves and spinal cord. Group 2 innate lymphoid cells (ILC2) are potent producers of type 2 cytokines that orchestrate immune and inflammatory responses. However, the role of ILC2 in CNS autoimmune diseases remains unknown. In patients with NMOSD, we identified a significant reduction of ILC2 in peripheral blood, which was correlated with disease severity. Using a mouse model of NMOSD induced by intracerebral injection of NMOSD-IgG with complement, we found CNS infiltration of ILC2 mainly expressing interleukin (IL)-5 and IL-13. The depletion of ILC2 led to increased CNS lesion volume, reduced CNS glucose metabolism, and augmented astrocyte injury and demyelination. The exacerbated NMOSD pathology was accompanied by increased accumulation of Iba1+ cells and complement activity in CNS lesions. In addition, the expansion of ILC2 using IL-33 attenuated NMO pathology. Collectively, these findings suggest a beneficial role of ILC2 in NMOSD, which deserves further investigation for future design of immune therapies to treat patients with NMOSD.
Keywords: CNS inflammation; autoimmunity; innate immunity; innate lymphoid cells; neuromyelitis optica.
© 2021 Federation of American Societies for Experimental Biology.