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Botryllus schlosseri as a Unique Colonial Chordate Model for the Study and Modulation of Innate Immune Activity

Journal

MARINE DRUGS
Volume 19, Issue 8, Pages -

Publisher

MDPI
DOI: 10.3390/md19080454

Keywords

immune tolerance; allorecognition; stem-cell transplantation; Botryllus schlosseri; tunicates; innate immunity; immune rejection; immune modulation

Funding

  1. Israel Science Foundation (ISF) [1416/19]
  2. HFSP Research Grant [RGY0085/2019]
  3. European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [948476]
  4. NIH [R21AG062948]
  5. Chan Zuckerberg investigator program
  6. European Research Council (ERC) [948476] Funding Source: European Research Council (ERC)

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Botryllus schlosseri, a colonial tunicate closest to vertebrates, lacks adaptive immunity but possesses unique characteristics making it a valuable model for studying innate immunity mechanisms. Studies in B. schlosseri have revealed a framework underlying the loss of tolerance to allogeneic tissues and provided insights into hematopoietic stem cell transplantation. Understanding the successful innate immune tolerance in B. schlosseri can potentially offer novel insights and modulations of immune processes in humans.
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.

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