Our results obtained in cell lines in vitro, not necessarily reflect what happens in vivo. Further, cell lines are transformed cells similar to tumor cells, in which EVs release has been associated to their biological features (i.e., malignant/benign) (50), suggesting even more caution in interpretation of data. Nevertheless, we reproduced our results also in primary cells, and pannexin-1 knockout mice develop a milder form of EAE (51). We showed, however, that pannexin-1 inhibition in vitro did not result in a reduction of ATP-induced MV release. Hence, in this case, the amelioration of the disease cannot be related to a variation of the MV number due to a modulation of exATP-related signaling.