The most recent Diablo 4 cinematic trailer from Blizzard showcases D2R Items facing down Lilith as well as armies at both their backs. Although this trailer does not show Tyrael's direct involvementin the story, his involvement in the creation of Horadrim and influence with the Paladins from Sanctuary suggests that he's involved. Light and dark battles in the battle, and the now-dead Tyrael lies somewhere between.
It is highly likely that his presence will be experienced through these intermediaries unless events force his hand. Tyrael is still dealing with the repercussions of the destruction of his Worldstone at the end of Diablo 2. This mystical object protected Sanctuary from Heaven and Hell and now serves as the protector of the area in its place. Tyrael does not appear likely to lead any further adventures into Hell or travel any further than the Pandemonium Fortress, where he could offer advice as Deckard Cain for those who choose to listen.
Five classes playable in Diablo have been revealed so far and all are variants of earlier games. With each of the games that has been released so far has brought something new to the table it is possible that Tyrael can be a player in the war that balances the sides, providing players with the possibility to be transformed into angels or demon-like abilities in exchange for duty to Sanctuary. This kind of strategy could easily follow on the multi-tree expansion that was previously announced for the series.
It seems unlikely that Blizzard intends to turn Angels and Demons into classes, since the series is centered around those who are caught between the two. However, as a mortal trapped between Heaven and Hell, Tyrael sits in an unusual position in Diablo legends. He will more likely be a balancing act in the tale, perhaps even the voice of reason rather than a side-lined player as previously. Even when forced to take sides buy d2r items, Tyrael is now aware of the true value of the mortals, and that is how he will most likely take part in the events of Diablo 4.