A2B adenosine receptor activation switches differentiation of bone marrow cells to a CD11c+Gr‐1+ dendritic cell subset that promotes the Th17 response. Issue 4 (30th July 2015)

• Record Type: Journal Article
• Authors: Liang, Dongchun; Zuo, Aijun; Shao, Hui; Chen, Mingjiazi; Kaplan, Henry J.; Sun, Deming
• Is Part Of: Immunity, inflammation and disease. Volume 3:Issue 4(2015)
• Page Start: 360
• Page End: 373
• Publication Date: 2015-07-30
• Subjects: Adenosine receptors -- autoimmunity -- experimental autoimmune uveitis -- γδ T cells -- IL‐17 -- Th17 -- uveitis; Immunology -- Periodicals; Immunity -- Periodicals; Inflammation -- Periodicals; 616.079
• DOI: 10.1002/iid3.74
• Languages: English
• ISSNs: 2050-4527

Abstract

Abstract: Adenosine is one of the major molecules associated with inflammation. We have previously reported that an adenosine receptor (AR) agonist has an enhancing effect on Th17 autoimmune responses, even though it suppressed Th1 responses. To determine the mechanism involved, we have examined the effect of AR agonists on mouse bone marrow dendritic cell (BMDC) differentiation and function. We show that mouse bone marrow cells (BMCs) differentiated into CD11c + Gr‐1 + dentritic cells (DCs) when cultured in granulocyte macrophage colony‐stimulating factor (GM‐CSF)‐containing medium containing an AR agonist. The non‐selective AR agonist NECA and an A2BR‐specific agonist had a similar effect, and the effect of NECA could be blocked by an A2BR‐specific antagonist. Unlike CD11c + Gr‐1 − BMDCs, which have a greater stimulatory effect on Th1 T cells than Th17 cells, CD11c + Gr‐1 + BMDCs had a greater stimulatory effect on Th17 autoreactive T cells than on Th1 autoreactive T cells and this effect depended on γδ T cell activation. Abstract : Adenosine receptor activation plays an important role in Th17 pathogenesis; Extracellular adenosine tips the balance of Th1 and Th17 responses; A2BR activation enhances Th17 pathogenesis via enhancing γδ T cell activation; A2BR agonist enhances Th17 response via activation of CD11c + Gr‐1 + DCs.