It is likely that his presence will be perceived D2R Items through these intermediaries unless events force his hand. Tyrael is still feeling the repercussions of destroying the Worldstone at the conclusion in Diablo 2. That mystical artifact protected Sanctuary from Heaven and Hell and now protects the land as its successor. Tyrael does not appear likely to lead any further expeditions to Hell or take his fight any further than to the Pandemonium Fortress, where he could provide advice like Deckard Cain to those who choose to listen.
Five classes playable in Diablo have been released so far and all of them are variants of earlier games. In the sense that each installment has introduced something new and exciting, maybe Tyrael could become a hand in the battle and help balance the sides by giving players the option to acquire angelic or demon-like powers to perform duties to Sanctuary. This type of mechanic could be a natural progression from the multi-tree expansion that was previously made public for the series.
It is unlikely that Blizzard will make Angels and Demons into classes, considering that the game's focus is on those stuck between them. However, as the only mortal in the middle of Heaven and Hell Tyrael finds himself in an unimaginable position in the entire Diablo history. He is more likely to be an equalizer in the story, or even as a voice of reason instead of taking sides like previously. Even when he is forced to take positions, Tyrael understands what is important to mortals. That is the way he is likely to play a role in the events buy diablo II resurrected items that unfold in Diablo 4.