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Disruption of Coronin 1 Signaling in T Cells Promotes Allograft Tolerance while Maintaining Anti-Pathogen Immunity

Jayachandran, Rajesh and Gumienny, Aleksandra and Bolinger, Beatrice and Ruehl, Sebastian and Lang, Mathias Jakob and Fucile, Geoffrey and Mazumder, Saumyabrata and Tchang, Vincent Sam Yong and Woischnig, Anne-Kathrin and Stiess, Michael and Kunz, Gabriele and Claudi, Beatrice and Schmaler, Mathias and Siegmund, Kerstin and Li, Jianping and Dertschnig, Simone and Hollaender, George and Medina, Eva and Karrer, Urs and Moshous, Despina and Bumann, Dirk and Khanna, Nina and Rossi, Simona W. and Pieters, Jean. (2019) Disruption of Coronin 1 Signaling in T Cells Promotes Allograft Tolerance while Maintaining Anti-Pathogen Immunity. Immunity, 50 (1). pp. 152-165.

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Biochemistry (Pieters)
UniBasel Contributors:Pieters, Jean and Bumann, Dirk
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
ISSN:1074-7613
e-ISSN:1097-4180
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:08 Feb 2020 15:06
Deposited On:06 Feb 2019 09:46

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