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Immunity. 2019 Jan 15;50(1):152-165.e8. doi: 10.1016/j.immuni.2018.12.011. Epub 2019 Jan 2.

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

Author information

1
Biozentrum, University of Basel, Basel, Switzerland. Electronic address: rajesh.jayachandran@unibas.ch.
2
Biozentrum, University of Basel, Basel, Switzerland.
3
Swiss Institute of Bioinformatics, sciCORE Computing Center, University of Basel, Basel, Switzerland.
4
Department of Biomedicine, University and University Hospital of Basel, Basel, Switzerland.
5
Novartis, Basel, Switzerland.
6
Department of Biomedicine, University and University Hospital of Basel, Basel, Switzerland; Department of Paediatrics, University of Oxford, Oxford, UK.
7
Helmholtz Center for Infection Research, Braunschweig, Germany.
8
Division of Infectious Diseases and Department of Medicine, Cantonal Hospital of Winterthur, Winterthur, Switzerland.
9
Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France and APHP Hôpital Universitaire Necker-Enfants Malades, Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Paris, France.
10
Department of Biomedicine, University and University Hospital of Basel, Basel, Switzerland; Division of Infectious Diseases, University and University Hospital of Basel, Switzerland.
11
Biozentrum, University of Basel, Basel, Switzerland. Electronic address: jean.pieters@unibas.ch.

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.

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