Dermal　fibrosis　is　characterized　by　collagen　accumulation　and　hyperproliferation　of　fibroblasts.　NLRC5,　as　the　largest　member　of　nucleotide-binding　domain　and　leucine-rich　repeat　(NLRs)　family,　has　recently　been　implicated　in　the　development　of　hepatic　fibrosis.　However,　the　role　of　NLRC5　in　dermal　fibrosis　remains　unknown.　Therefore,　herein,　we　investigated　the　effects　of　NLRC5　on　keloid　fibroblasts　(KFs)　and　transforming　growth　factor-beta　1　(TGF-beta　1)-induced　collagen　expression　and　explored　the　underlying　mechanism.　We　observed　that　NLRC5　mRNA　and　protein　levels　were　highly　expressed　in　KFs,　silencing　NLRC5　greatly　suppressed　TGF-beta　1-induced　KFs　proliferation.　Silencing　NLRC5　also　obviously　inhibited　the　expression　of　type　I　collagen,　CTGF　and　alpha-smooth　muscle　actin　(alpha-SMA)　in　human　KFs　induced　by　TGF-beta　1,　as　well　as　the　expression　of　TGF-beta　receptor　I　and　II.　Furthermore,　silencing　NLRC5　suppressed　the　expression　of　TGF-beta　1-induced　Smad2　and　Smad3　phosphorylation　in　human　KFs.　Taken　together,　our　study　suggest　that　silencing　NLRC5　reduced　ECM　expression　in　KFs　through　inhibiting　the　TGF-beta　1/Smad　signaling　pathway.　Therefore,　NLRC5　may　represent　a　promising　target　for　treatment　of　the　keloid　disease.　(C)　2016　Elsevier　Masson　SAS.　All　rights　reserved.