title: A2B adenosine receptor activation switches differentiation of bone marrow cells to a CD11c(+)Gr-1(+) dendritic cell subset that promotes the Th17 response.
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.
authors.affiliation: Department of Ophthalmology of the University of California Los Angeles Doheny Eye Institute California 90033 USA.
authors.forename: Dongchun
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Ophthalmology of the University of California Los Angeles Doheny Eye Institute California 90033 USA.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zuo
authors.affiliation: Department of Ophthalmology and Visual Sciences Kentucky Lions Eye Center University of Louisville Louisville Kentucky 40202 USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Ophthalmology of the University of California Los Angeles Doheny Eye Institute California 90033 USA.
authors.forename: Mingjiazi
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology and Visual Sciences Kentucky Lions Eye Center University of Louisville Louisville Kentucky 40202 USA.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.affiliation: Department of Ophthalmology of the University of California Los Angeles Doheny Eye Institute California 90033 USA.
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
keywords: Adenosine receptors; IL‐17; Th17; autoimmunity; experimental autoimmune uveitis; uveitis; γδ T cells