Abstract
Understanding the mechanisms that sustain immunological nonreactivity is essential for maintaining tissue in syngeneic and allogeneic settings, such as transplantation and pregnancy tolerance. While most transplantation rejections occur due to the adaptive immune response, the proinflammatory response of innate immunity is necessary for the activation of adaptive immunity. Botryllus schlosseri, a colonial tunicate, which is the nearest invertebrate group to the vertebrates, is devoid of T- and B-cell-based adaptive immunity. It has unique characteristics that make it a valuable model system for studying innate immunity mechanisms: (i) a natural allogeneic transplantation phenomenon that results in either fusion or rejection; (ii) whole animal regeneration and noninflammatory resorption on a weekly basis; (iii) allogeneic resorption which is comparable to human chronic rejection. Recent studies in B. schlosseri have led to the recognition of a molecular and cellular framework underlying the innate immunity loss of tolerance to allogeneic tissues. Additionally, B. schlosseri was developed as a model for studying hematopoietic stem cell (HSC) transplantation, and it provides further insights into the similarities between the HSC niches of human and B. schlosseri. In this review, we discuss why studying the molecular and cellular pathways that direct successful innate immune tolerance in B. schlosseri can provide novel insights into and potential modulations of these immune processes in humans.
Highlights
The study of the immunological mechanisms that allow animals to regenerate and to recognize allogeneic tissues is an important trait in the field of transplantation
B. schlosseri was developed as a model for studying hematopoietic stem cell (HSC) transplantation, and it provides further insights into the similarities between the HSC niches of human and B. schlosseri
These data confirm that the process of allogeneic resorption comprises different crosstalk events which can be further studied in B. schlosseri
Summary
The study of the immunological mechanisms that allow animals to regenerate and to recognize allogeneic tissues is an important trait in the field of transplantation. B. schlosseri has been studied for decades and has very interesting natural phenomena which are based on innate immune responses, from natural transplantation or rejection to synchronized program cell removal and whole-body regeneration. Of zooids and the allogeneic resorption (detailed in part E) that takes place in B. schlosseri chimeras share similarities in the immune response, as both involve the constant crosstalk among apoptosis, self/nonself recognition, and phagocytosis [62] As this crosstalk occurs under natural conditions, B. schlosseri represents a valuable model to study, at different levels (genes, metabolites, signaling molecules, and cellular functions), the mechanisms that guide programmed cell removal, which enables the regeneration of new zooids
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