Journal
IMMUNITY
Volume 50, Issue 1, Pages 152-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2018.12.011
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Funding
- Cloetta foundation
- Swiss Life fellowship
- HSFP fellowship
- Marie Vogt Heim Fellowship
- Lise Meitner position of the FWF Austrian Science Fund
- Swiss National Science Foundation
- Gebert Ruef Foundation
- Swiss MS Society
- Canton of Basel
- SIB Swiss Institute of Bioinformatics
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The ability of the immune system to discriminate self from non-self is essential for eradicating microbial pathogens but is also responsible for allograft rejection. Whether it is possible to selectively suppress alloresponses while maintaining anti-pathogen immunity remains unknown. We found that mice deficient in coronin 1, a regulator of naive T cell homeostasis, fully retained allografts while maintaining T cell-specific responses against microbial pathogens. Mechanistically, coronin 1-deficiency increased cyclic adenosine monophosphate (cAMP) concentrations to suppress allo-specific T cell responses. Costimulation induced on microbe-infected antigen presenting cells was able to overcome cAMP-mediated immunosuppression to maintain anti-pathogen immunity. In vivo pharmacological modulation of this pathway or a prior transfer of coronin 1-deficient T cells actively suppressed allograft rejection. These results define a coronin 1-dependent regulatory axis in T cells important for allograft rejection and suggest that modulation of this pathway may be a promising approach to achieve long-term acceptance of mismatched allografts.
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