Beyond ecto-nucleotidase: CD39 defines human Th17 cells with CD161

Abstract

CD39/ENTPD1 is a prototypic member of the ectonucleoside triphosphate diphosphohydrolase (ENTPDase) family on cell surface. CD39 has been reported to be a marker of regulatory immune cells and catalyzes extracellular hydrolysis of nucleotides to generate AMP and, in tandem with CD73, adenosine. We have recently found in addition that co-expression of CD39 and CD161 by human CD4 + T cells may become a biomarker of human Th17 cells. CD39 and CD161 have direct interactions that are further linked with acid sphingomyelinase (ASM). Upon activation of CD39 and CD161, the molecular interactions boost ASM bio-activity, which generates cellular ceramide to further mediate downstream signals inclusive of STAT3 and mTOR. We suggest modulation of human Th17 responsiveness by CD39 and CD161 and describe novel molecular mechanisms integrating elements of both extracellular nucleotide and sphingolipid homeostasis that are pivotal in the control of human Th17 cells and which could have therapeutic potential.

Tumor-infiltrating CD39+γδTregs are novel immunosuppressive T cells in human colorectal cancer

“…A recent study shows that CD39 is only a surface marker and does not have function 17 , whereas other study indicates that co-expression of CD39 and CD161 on human Th17 cells can boost sphingomyelinase bioactivity to mediate downstream signals including STAT3 and mTOR, suggesting that CD39 is a functional marker on human Th17 cells. 45 In addition, a recent study suggests that CD39 is a marker for human exhausted CD8 C T cells possibly due to ectonucleotidase. 46 In this study, we show that CD39 is highly expressed on tumor-infiltrating gdT cells.…”

Anti-CD20 Antibodies for Idiopathic Nephrotic Syndrome in Children

“…In particular, B cells may act at several levels of the immune response: They modulate adaptive immunity and regulate the T-cell compartment via CD80 and CTLA4; CD80 is a costimulatory molecule expressed by antigen-presenting cells and by B cells (6). Via SMPDL-3b/ASM, rituximab also modulates IL-17 production by Th17; CD39 and CD161 may serve as surface markers of IL-17 and modulate, in turn, ASM SMPDL-3b-mediated signal transduction (STAT3) (44). Finally, by interacting with SMPDL-3b/ASM in podocytes, rituximab may stabilize actin remodeling, which is a mechanism for proteinuria (42).…”

Purinergic Signaling Receptors Expression on Peripheral T-Lymphocytes of Healthy Donors

“…В периферической крови и биоптатах слизистых оболочек больных с болезнью Крона уровень этих клеток был сущест-венного выше такового условно здоровых доноров. Причем оценка относительного содержания клеток данной субпопуляции Т-хелперов в крови боль-ных позволяла отличить активную форму болезни Крона от неактивной, что позволяет использовать оценку уровня CD39+CD161+CD4+ клеток в диаг-ностических целях [32].…”