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Disruption of Coronin 1 Signaling in T Cells Promotes Allograft Tolerance while Maintaining Anti-Pathogen Immunity.
Jayachandran, Rajesh Gumienny, Aleksandra Bolinger, Beatrice Ruehl, Sebastian Lang, Mathias Jakob Fucile, Geoffrey Mazumder, Saumyabrata Tchang, Vincent Woischnig, Anne-Kathrin Stiess, Michael
Jayachandran, Rajesh
Gumienny, Aleksandra
Bolinger, Beatrice
Ruehl, Sebastian
Lang, Mathias Jakob
Fucile, Geoffrey
Mazumder, Saumyabrata
Tchang, Vincent
Woischnig, Anne-Kathrin
Stiess, Michael
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2019-01-02
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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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Immunity. 2019;50(1):152-165.e8. doi:10.1016/j.immuni.2018.12.011.
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en
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1097-4180
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Attribution-NonCommercial-ShareAlike 4.0 International