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CCL20/CCR6 chemokine signaling is not essential for pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis

Sachi, N;Kamiyama, N;Saechue, B;Ozaka, S;Dewayani, A;Ariki, S;Chalalai, T;Soga, Y;Fukuda, C;Kagoshima, Y;Ekronarongchai, S;Kobayashi, T;

Multiple sclerosis is an autoimmune disease in which the immune system attacks the nerve myelin sheath. The balance between pathogenic Th17 cells and regulatory Treg cells, both of which express the chemokine receptor CCR6 is critical for determining disease activity. It has been postulated that CCL20, the cognate ligand of CCR6, produced by the blood-brain barrier attracts these immune cells to the central nervous system (CNS). However, the pathological phenotypes of the experimental model of multiple sclerosis in CCR6-knockout (KO) mice are inconclusive, while this has not been addressed in CCL20-KO mice.

To address this, we generated CCL20-KO and CCR6-KO mice using the CRISPR/Cas9 system. Clinical phenotypes of experimental autoimmune encephalomyelitis (EAE) in the chronic phase were slightly exacerbated in both mutant mice relative to those in wild-type (WT) mice. Inflammatory cell infiltration and demyelination in the CNS were similar in the KO and WT mice. CNS CD4+ T cell counts were the same for mutant and WT mice. The mutant and WT mice did not differ significantly in the proportions of Th17 and Treg cells in the CNS, or in IL-17 and TGF-β mRNA expression in the CNS.

These findings suggest that CCL20/CCR6-mediated cell migration is not necessarily required for the onset of EAE, and may be compensated for by other chemokine signals.