Salamanders don't need immune defenses to regrow limbs, study finds
Researchers created immune-deficient newts that regenerate appendages just as well as normal animals, suggesting adaptive immunity actually slows the process. The finding could redirect regenerative medicine research away from immune suppression and toward other molecular pathways, potentially accelerating development of therapies for human tissue repair.
Originaltitel: Adaptive immunity is dispensable for salamander appendage regeneration
Abstract Complex multi-tissue regeneration capacity varies across vertebrates. Mammals are amongst the least regenerative species, while salamanders can regenerate complex tissues such as limbs and tails throughout life. Previous studies have shown that innate and adaptive immune cells are present during salamander limb regeneration. While innate immune cells have been shown to promote limb regeneration, it is unknown whether adaptive immunity is responsive to amputation or plays a role in appendage regeneration. Here we show that during limb regeneration in axolotls, the immune response is characterized by a coordinated immunoregulatory signature including the downregulation of antigen presentation, cytokine secretion, and T cell activation. To test the role of adaptive immune cells in regeneration, we generated Recombination activating gene 1 deficient ( Rag1 −/− ) newts. Rag1 −/− newts lack antigen receptor recombination and show a marked reduction of adaptive immune cells. We find that Rag1 −/− newts do not reject allografts, confirming their functional immunodeficiency. Finally, we demonstrate that both larval and adult newts regenerate appendages in the absence of adaptive immunity. Our work demonstrates that the adaptive arm of the immune system is not required for appendage regeneration and establishes an important model for novel experimental approaches in comparative immunology and regenerative biology.