Induction of antiinflammatory purinergic signaling in activated human iNKT cells. JCI Insight 2018 Sep 06;3(17)
Date
09/07/2018Pubmed ID
30185656Pubmed Central ID
PMC6171811DOI
10.1172/jci.insight.91954Scopus ID
2-s2.0-85062248182 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
Invariant natural killer T (iNKT) cells are activated at sites of local tissue injury, or globally during vaso-occlusive episodes of sickle cell disease (SCD). Tissue damage stimulates production of CD1d-restricted lipid antigens that activate iNKT cells to produce Th1- and Th2-type cytokines. Here, we show that circulating iNKT cells in SCD patients express elevated levels of the ectonucleoside triphosphate diphosphosphohydrolase, CD39, as well the adenosine A2A receptor (A2AR). We also investigated the effects of stimulating cultured human iNKT cells on the expression of genes involved in the regulation of purinergic signaling. iNKT cell stimulation caused induction of ADORA2A, P2RX7, CD38, CD39, ENPP1, CD73, PANX1, and ENT1. Transcription of ADA, which degrades adenosine, was reduced. Induction of CD39 mRNA was associated with increased ecto-ATPase activity on iNKT cells that was blocked by POM1. Exposure of iNKT cells to A2AR agonists during stimulation reduced production of IFN-γ and enhanced production of IL-13 and CD39. Based on these findings, we define "purinergic Th2-type cytokine bias" as an antiinflammatory purinergic response to iNKT cell stimulation resulting from changes in the transcription of several genes involved in purine release, extracellular metabolism, and signaling.
Author List
Yu JC, Lin G, Field JJ, Linden JAuthor
Joshua J. Field MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
5'-NucleotidaseADP-ribosyl Cyclase 1
Anemia, Sickle Cell
Antigens, CD1d
Apyrase
Connexins
Cytokines
Equilibrative Nucleoside Transporter 1
GPI-Linked Proteins
Humans
Immunity, Innate
Interleukin-13
Natural Killer T-Cells
Nerve Tissue Proteins
Phosphoric Diester Hydrolases
Purinergic Agents
Purines
Pyrophosphatases
Receptor, Adenosine A2A
Receptors, Purinergic P2X7
Signal Transduction
Transcription Factors
