Extracellular adenosine regulates colitis through effects on lymphoid and nonlymphoid cells

CC Kurtz, I Drygiannakis… - American Journal …, 2014 - journals.physiology.org
CC Kurtz, I Drygiannakis, M Naganuma, S Feldman, V Bekiaris, J Linden, CF Ware, PB Ernst
American Journal of Physiology-Gastrointestinal and Liver …, 2014journals.physiology.org
Adenosine is a purine metabolite that can mediate anti-inflammatory responses in the
digestive tract through the A2A adenosine receptor (A2AAR). We examined the role of this
receptor in the control of inflammation in the adoptive transfer model of colitis. Infection of
A2AAR−/− mice with Helicobacter hepaticus increased colonic inflammation scores
compared with uninfected A2AAR controls. Comparison of T cell subsets in wild-type and
A2AAR−/− mice revealed differences in markers associated with activated helper T (Th) cells …
Adenosine is a purine metabolite that can mediate anti-inflammatory responses in the digestive tract through the A2A adenosine receptor (A2AAR). We examined the role of this receptor in the control of inflammation in the adoptive transfer model of colitis. Infection of A2AAR−/− mice with Helicobacter hepaticus increased colonic inflammation scores compared with uninfected A2AAR controls. Comparison of T cell subsets in wild-type and A2AAR−/− mice revealed differences in markers associated with activated helper T (Th) cells and regulatory T (Treg) cells. Previous studies showed that expression of A2AAR on CD45RBHI and CD45RBLO Th cells is essential for the proper regulation of colonic inflammation. Adoptive transfer of CD45RBHI with CD45RBLO from wild-type mice into RAG1−/−/A2AAR−/− mice induced severe disease within 3 wk, although transfer of the same subsets into RAG1−/− mice does not induce colitis. This suggests that the presence of A2AAR on recipient cells is also important for controlling colitis. To investigate the role of A2AAR in myeloid cells, chimeric recipients were generated by injection of bone marrow from RAG1−/− or RAG1−/−/A2AAR−/− mice into irradiated RAG1−/− mice. After adoptive transfer, these recipients did not develop colitis, regardless of A2AAR expression by the donor. Together, our results suggest that the control of inflammation in vivo is dependent on A2AAR signaling through multiple cell types that collaborate in the regulation of colitis by responding to extracellular adenosine.
American Physiological Society