Adenosine primes resting stage dendritic cells before their activation.
The effect of adenosine mediated suppression of immune cell activation has long been an important topic of study. While the protective benefits of such a signaling mechanism are well recognized, there remains a question as to how dendritic cells (DCs) bypass the high levels of adenosine during tissue stress and infection, and become fully activated. We report here that adenosine receptors on resting stage DCs, both in vivo and in vitro, are functionally desensitized after ligand binding. This desensitization lasts several hours during which DCs are "blind" to adenosine and are stimulated without this negative feedback. This effect is mediated by cAMP signaling. Our report suggests that there is a specific regulatory mechanism used by DCs to overcome adenosine mediated inhibition to become fully activated despite a general suppressive state.
Flach
Tracy L
TL
Immunology Research Group & Department of Microbiology and Infectious Diseases, 4A18 HRIC, 3330 Hospital Dr. NW, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Pang
Winston
W
Chau
Elaine M T
EM
Desrosiers
Melanie D
MD
Shi
Yan
Y