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Here we determined the effects of macrophage derived exosomes regarding the improvement EAN in Lewis rats. M1 macrophage derived exosomes (M1 exosomes) were discovered to aggravate EAN via improving Th1 and Th17 reaction, while M2 macrophage derived exosomes (M2 exosomes) showed potentials to mitigate infection extent via a mechanism bypassing Th1 and Th17 response. Besides, both M1 and M2 exosomes increased germinal center responses in EAN. More in vitro studies confirmed that M1