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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discovery 11:763–776
van Beelen AJ, Zelinkova Z, Taanman-Kueter EW, Muller FJ, Hommes DW, Zaat SA, Kapsenberg ML, de Jong EC (2007) Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity 27:660–669
Kleinschek MA, Boniface K, Sadekova S, Grein J, Murphy EE, Turner SP, Raskin L, Desai B, Faubion WA, de Waal Malefyt R, Pierce RH, McClanahan T, Kastelein RA (2009) Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation. J Exp Med 206:525–534
Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB, Robson SC (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204:1257–1265
Zhou Q, Yan J, Putheti P, Wu Y, Sun X, Toxavidis V, Tigges J, Kassam N, Enjyoji K, Robson SC, Strom TB, Gao W (2009) Isolated CD39 expression on CD4+ T cells denotes both regulatory and memory populations. Am J Transplant 9:2303–2311
Dwyer KM, Hanidziar D, Putheti P, Hill PA, Pommey S, McRae JL, Winterhalter A, Doherty G, Deaglio S, Koulmanda M, Gao W, Robson SC, Strom TB (2010) Expression of CD39 by human peripheral blood CD4+ CD25+ T cells denotes a regulatory memory phenotype. Am J Transplant 10:2410–2420
Bai A, Moss A, Kokkotou E, Usheva A, Sun X, Cheifetz A, Zheng Y, Longhi MS, Gao W, Wu Y, Robson SC (2014) CD39 and CD161 modulate Th17 responses in Crohn’s disease. J Immunol 193:3366–3377
Pozo D, Vales-Gomez M, Mavaddat N, Williamson SC, Chisholm SE, Reyburn H (2006) CD161 (human NKR-P1A) signaling in NK cells involves the activation of acid sphingomyelinase. J Immunol 176:2397–2406
Acknowledgments
This study was supported by funds from the National Institute of Health (NHLBI PO1-HL076540 and RO1-HL094400) and National Natural Science Foundation of China (No. 81470828, 81270472, and 81070310).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bai, A., Robson, S. Beyond ecto-nucleotidase: CD39 defines human Th17 cells with CD161. Purinergic Signalling 11, 317–319 (2015). https://doi.org/10.1007/s11302-015-9457-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11302-015-9457-4