title: 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.affiliation: Digestive Health Center of Excellence, University of Virginia, Charlottesville, Virginia;
authors.forename: Courtney C
authors.initials: CC
authors.lastname: Kurtz
authors.affiliation: Center for Veterinary Sciences and Comparative Medicine, University of California, San Diego, La Jolla, California; Division of Comparative Pathology and Medicine, Department of Pathology, University of California, San Diego, La Jolla, California;
authors.forename: Ioannis
authors.initials: I
authors.lastname: Drygiannakis
authors.affiliation: Digestive Health Center of Excellence, University of Virginia, Charlottesville, Virginia;
authors.forename: Makoto
authors.initials: M
authors.lastname: Naganuma
authors.affiliation: Center for Comparative Medicine, University of Virginia, Charlottesville, Virginia;
authors.forename: Sanford
authors.initials: S
authors.lastname: Feldman
authors.affiliation: Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, California; and.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Bekiaris
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, California.
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.affiliation: Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, California; and.
authors.forename: Carl F
authors.initials: CF
authors.lastname: Ware
authors.affiliation: Center for Veterinary Sciences and Comparative Medicine, University of California, San Diego, La Jolla, California; Division of Comparative Pathology and Medicine, Department of Pathology, University of California, San Diego, La Jolla, California; pernst@ucsd.edu.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Ernst
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003092:Colitis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D044923:Helicobacter hepaticus / Q000472:pathogenicity; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000235:genetics; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018398:Homeodomain Proteins; D018836:Inflammation Mediators; D043705:Receptor, Adenosine A2A; C064658:RAG-1 protein; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D000241:Adenosine
keywords: A2A adenosine receptor; adenosine; adoptive transfer; colitis; regulatory T cells