Evaluating the compatibility of adaptive immunity and complex tissue regeneration

It remains an open question why select animals have the ability to regenerate complex multi-tissue structures (e.g., limbs). A longstanding theory in the field of regenerative biology is that the adaptive immune system impedes regeneration.

Supporting a potential negative role for adaptive immunity, we have uncovered evidence that the regenerative microenvironment may itself be immunosuppressive.

A lack of tools available in species with high regenerative capacity has made it impossible to test for a potential causative relationship between dampened adaptive immunity and regeneration.

Pairing highly regenerative organisms, like salamanders, with novel molecular tools and classic immunological assays, we are now primed to test this unresolved theory regarding the immune system´s role in regenerative capacity.

This proposal will apply immunologic assays to determine the immunomodulatory nature of the cells of the regenerative niche.

We will also perform a loss-of-function CRISPR screen to identify key components of adaptive immune responses in salamanders.

We will culminate in experiments directly testing the compatibility of robust adaptive immune responses and complex tissue regeneration.

This proposal will provide fundamental insights into the compatibility of complex tissue regeneration and adaptive immunity. In the long term, we aspire to harness the immune system to improve regenerative outcomes.