Joe Schmidt has elected to shuffle the pack for Ireland's trip to Italy on Sunday.
Jordi Murphy, Ultan Dillane, Sean Cronin, and Dave Kilcoyne will all start in Rome against Conor O'Shea's hosts.
Rory Best, Jack Conan, James Ryan, and Cian Healy have all been rested by Schmidt after the win over Scotland in Murrayfield last time out.
Dillane, Cronin (who has 67 caps), and Kilcoyne are all set to start a Six Nations match for the first time, while Murphy slots in for the injured Stander, with Jack Conan not yet ready to return.
All four changes come in the forwards, with the backs remaining unchanged.
Peter O'Mahony will captain the team in Best's absence. Best had previously started 60 of Ireland's 61 Six Nation matches since 2007.
Joey Carbery misses out on the squad due to a hamstring injury, but Chris Farrell has shaken off a minor injury to maintain his place in the starting fifteen.
Italy captain Sergio Parisse misses out for the home side after suffering a concussion for Stade Francais last week. Irishman Ian McKinley has been named on the bench for O'Shea's side.
The Italians have lost a record 19 consecutive Six Nations games since beating Scotland in 2013. They have lost 87 of their 99 matches in the competition, with Saturday's meeting with Ireland marking 100 games in the tournament.
Kick-off is at 3pm in Rome on Sunday.
Italy team: 15 Jayden Hayward, 14 Edoardo Padovani, 13 Michele Campagnaro, 12 Luca Morisi, 11 Angelo Esposito, 10 Tommaso Allan, 9 Tito Tebaldi; 1 Andrea Lovotti, 2 Leonardo Ghiraldini (c), 3 Simone Ferrari, 4 Federico Ruzza, 5 Dean Budd, 6 Jimmy Tuivaiti, 7 Maxime Mbanda, 8 Braam Steyn. Replacements: 16 Luca Bigi, 17 Cherif Traore, 18 Tiziano Pasquali, 19 David Sisi, 20 Alessandro Zanni, 21 Guglielmo Palazzani, 22 Ian McKinley, 23 Tommaso Castello.
Ireland team: 15 Rob Kearney, 14 Keith Earls, 13 Chris Farrell, 12 Bundee Aki, 11 Jacob Stockdale, 10 Johnny Sexton, 9 Conor Murray; 1 Dave Kilcoyne, 2 Sean Cronin, 3 Tadhg Furlong, 4 Ultan Dillane, 5 Quinn Roux, 6 Peter O'Mahony (c), 7 Sean O'Brien, 8 Jordi Murphy.