Johnny Sexton returns to captain Ireland in Saturday's Six Nations game in Rome as Andy Farrell's side shows seven changes from the France defeat.
While Sexton has recovered from a head knock, Conor Murray remains out as Jamison Gibson-Park again starts.
Jordan Larmour replaces Keith Earls on the wing.
Dave Kilcoyne, Ronan Kelleher and Tadhg Furlong form a new front row with fit-again James Ryan and Will Connors also drafted into the pack.
Lock Ryan's inclusion sees Tadhg Beirne switching to the back row as Rhys Ruddock and Josh van der Flier drop out of the match day 23 after starting against France.
Kilcoyne, Kelleher and Furlong take over from Cian Healy, Rob Herring and Andrew Porter who are named on the bench.
Sexton's regular half-back partner Murray remains unavailable because of the hamstring injury picked up in training during the week of the France game.
Skipper Sexton, now 35, appeared to hint earlier this week that he might not continue playing up to the 2023 World Cup in France but later said that his utterance had just been a "throwaway comment".
Ireland coach Farrell said he believes Sexton's appetitive "is as strong as ever" after selecting the Leinster veteran for his 97th cap.
"As long as Johnny keeps on giving to Irish rugby, he'll keep putting his foot forward to be in the equation, won't he? He feels good at this moment in time," said the Ireland coach.
Sexton said earlier in the week that he had "nearly" agreed a one-year contract extension with the IRFU and Farrell said "both sides are happy with those conversations".
Ulster fly-half Billy Burns edges out Leinster's Ross Byrne for the fly-half replacement berth while Munster scrum-half Craig Casey and Leinster lock Ryan Baird are in line for first caps after being named on a bench which also includes wing Earls.
Casey was in the replacements for the France game but did not come on.
Robbie Henshaw will earn his 50th cap after being retained at centre alongside his Leinster team-mate Garry Ringrose.
Italy earned Rome win over Irish in 2013
Ireland go into Saturday's game badly in need of a win after losing their first two opening games for the first time since the tournament became the Six Nations with the addition of the Italians.
Coach Farrell denied that there was any sense of risk in picking a totally changed front row.
"The three that come in have been working together in training the last few weeks so there some continuity in that regard," Farrell said.
"Ronan [Kelleher] deserves a start. His attitude has been first class in training."
Italy, who last beat Ireland in 2013, will be aiming to avoid a 30th straight Six Nations defeat but Farrell insisted they are an improving outfit.
"I certainly feel they're good enough to stay in the competition long term. I can see the progress Franco [Smith] is making with them. They are certainly heading in the right direction."
Line-up
Ireland: Keenan; Larmour, Ringrose, Henshaw, Lowe; Sexton, Gibson-Park; Kilcoyne, Kelleher, Furlong; Henderson, Ryan (capt); Beirne, Connors, Stander.
Replacements: Herring, Healy, Porter, Baird, Conan, Casey, Burns, Earls.