Extracellular adenosine regulates colitis through effects on lymphoid and nonlymphoid cells.

Abstract

Adenosine is a purine metabolite that can mediate anti-inflammatory responses in the digestive tract through the A(2A) adenosine receptor (A(2A)AR). We examined the role of this receptor in the control of inflammation in the adoptive transfer model of colitis. Infection of A(2A)AR(-/-) mice with Helicobacter hepaticus increased colonic inflammation scores compared with uninfected A(2A)AR controls. Comparison of T cell subsets in wild-type and A(2A)AR(-/-) mice revealed differences in markers associated with activated helper T (Th) cells and regulatory T (Treg) cells. Previous studies showed that expression of A(2A)AR on CD45RB(HI) and CD45RB(LO) Th cells is essential for the proper regulation of colonic inflammation. Adoptive transfer of CD45RB(HI) with CD45RB(LO) from wild-type mice into RAG1(-/-)/A(2A)AR(-/-) 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 A(2A)AR on recipient cells is also important for controlling colitis. To investigate the role of A(2A)AR in myeloid cells, chimeric recipients were generated by injection of bone marrow from RAG1(-/-) or RAG1(-/-)/A(2A)AR(-/-) mice into irradiated RAG1(-/-) mice. After adoptive transfer, these recipients did not develop colitis, regardless of A(2A)AR expression by the donor. Together, our results suggest that the control of inflammation in vivo is dependent on A(2A)AR signaling through multiple cell types that collaborate in the regulation of colitis by responding to extracellular adenosine.

• Authors: Courtney C Kurtz, Ioannis Drygiannakis, Makoto Naganuma, Sanford Feldman, Vasileios Bekiaris, Joel Linden, Carl F Ware, Peter B Ernst
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 307 Issue 3 Pg. G338-46 (Aug 01 2014) ISSN: 1522-1547 [Electronic] United States
• PMID: 24875104 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• Biomarkers
• Cytokines
• Homeodomain Proteins
• Inflammation Mediators
• Receptor, Adenosine A2A
• RAG-1 protein
• Leukocyte Common Antigens
• Ptprc protein, mouse
• Adenosine

Topics

• Adenosine (metabolism)
• Adoptive Transfer
• Animals
• Biomarkers (metabolism)
• Colitis (immunology, metabolism, microbiology, prevention & control)
• Colon (immunology, metabolism, microbiology)
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• Helicobacter hepaticus (pathogenicity)
• Homeodomain Proteins (genetics, metabolism)
• Inflammation Mediators (metabolism)
• Leukocyte Common Antigens (metabolism)
• Lymph Nodes (immunology, metabolism, microbiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptor, Adenosine A2A (deficiency, genetics)
• Severity of Illness Index
• T-Lymphocyte Subsets (immunology, metabolism, microbiology, transplantation)
• T-Lymphocytes, Helper-Inducer (immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Time Factors