The keratin-related Ouroboros proteins function as immune antigens mediating tail regression in Xenopus metamorphosis

Abstract

Tail resorption during amphibian metamorphosis has been thought to be controlled mainly by a cell-autonomous mechanism of programmed cell death triggered by thyroid hormone. However, we have proposed a role for the immune response in metamorphosis, based on the finding that syngeneic grafts of tadpole tail skin into adult Xenopus animals are rejected by T cells. To test this, we identified two tail antigen genes called ouro1 and ouro2 that encode keratin-related proteins. Recombinant Ouro1 and Ouro2 proteins generated proliferative responses in vitro in T cells isolated from naive adult Xenopus animals. These genes were expressed specifically in the tail skin at the climax of metamorphosis. Overexpression of ouro1 and ouro2 induced T-cell accumulation and precocious tail degeneration after full differentiation of adulttype T cells when overexpressed in the tail region. When the expression of ouro1 and ouro2 were knocked down, tail skin tissue remained even after metamorphosis was complete. Our findings indicate that Ouro proteins participate in the process of tail regression as immune antigens and highlight the possibility that the acquired immune system contributes not only to self-defense but also to remodeling processes in vertebrate morphogenesis.amphibian ͉ skin ͉ cell death ͉ T cell ͉ remodeling

How Do Lampreys Avoid Cholestasis After Bile Duct Degeneration?

“…Mack et al proposed that bile duct infection or injury due to rotavirus infection could be inciting factors leading to progressive, autoimmune-mediated damage of the biliary tree after recovery from infection (Mack & Sokol, 2005;Barnes et al, 2009). Incidentally, it has been revealed that programmed cell death in amphibian metamorphosis is induced by a selective auto-immune response, and that the immune system may contribute to the remodeling processes in vertebrate morphogenesis, universally (Mukaigasa et al, 2009). The onset of human BA always occurs during the pre-natal or perinatal periods despite the fact that rotavirus infection with acholic stool and other viral infections are so common among preschool children and infants under one year of age.…”

The genus Xenopus as a multispecies model for evolutionary and comparative immunobiology of the 21st century

“…The role of the immune system in tail physiology becomes even more complex at pre-metamorphic and metamorphic stages when the tail is resorbed. Although tail degeneration is usually thought to be controlled mainly by a cell-autonomous mechanism of programmed cell death triggered by thyroid hormone, a critical involvement of the immune system has been shown [29]. Two keratin proteins, Ouro1 and Ouro2 proteins, specifically expressed in the tail skin, are necessary and sufficient to promote T cell-mediated tail regression.…”

Mechanisms of tail resorption during anuran metamorphosis

“…These results strongly suggest that the tadpole immune system recognizes tail-skin-specific Ouro1/2 proteins as larval antigens during the metamorphosis climax, and the recognition is pivotal to tail resorption. This immunological rejection model suggests that newly differentiated adult-type immune cells recognize Ouro proteins as non-self targets for tail dissolution, allowing the elimination of larval cells during metamorphosis (35).…”