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

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

The DNA damage response—Repair or despair?

The term “the DNA damage response” (DDR) encompasses a sophisticated array of cellular initiatives set in motion as cells are exposed to DNA-damaging events. It has been known for over half a century that all organisms have the ability to restore genomic integrity through DNA repair. More recent discoveries of signal transduction pathways linking DNA damage to cell cycle arrest and apoptosis have greatly expanded our views of how cells and tissues limit mutagenesis and tumorigenesis. DNA repair not only plays a pivotal role in suppressing mutagenesis but also in the reversal of signals inducing the stress response. If repair is faulty or the cell is overwhelmed by damage, chances are that the cell will despair and be removed by apoptosis. This final fate is determined by intricate cellular dosimeters that are yet to be fully understood. Here, key findings leading to our current view of DDR are discussed as well as potential areas of importance for future studies. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78214/1/20597_ftp.pd

Li'l boy love.

Gift of Dr. Mary Jane Esplen.Piano vocal ukulele [instrumentation]E flat major [key]Moderato [tempo]Popular song ; film musical [form/genre]Photograph: belles, Lillian Cornell [illustration]Biography of Earl Carroll back cover [note]Publisher's advertisement on front inside cover [note

Moon over Burma.

Gift of Dr. Mary Jane Esplen.Piano vocal guitar uke [instrumentation]E flat major [key]Molto Moderato [tempo]Popular song [form/genre]Photo: Dorothy Lamour [illustration]Blurb about Francis Craig [note]Publisher's advertisement on front inside cover [note