Abstract
As the rate-limiting enzyme in ATP/ADP–AMP–adenosine pathway, CD39 would be a novel checkpoint inhibitor target in preventing adenosine-triggered immune-suppressive effect. In addition, CD39hi Tregs, but not CD25hi Tregs, exhibit sustained Foxp3 levels and functional abilities, indicating it could represent a new specific marker of Tregs. Similarly, inhibition of CD39 enzymatic function at the surface of tumor cells alleviates their immunosuppressive activity. Far from conclusive, present research revealed that CD39 also dephosphorylated and thus inactivated self- and pathogen-associated phosphoantigens of Vγ9Vδ2 T cells, which may be the most promising subpopulation for cellular vaccine. CD39 is also tightly related to Th17 cells and can be regarded as a Th17 cells marker. In this review, we focus on present research of CD39 ectoenzyme and provide insights into its clinical application.
Highlights
Extracellular adenosine and ATP exert important functions in physiology and pathophysiology
Some recent research has revealed a number of neoteric functions of CD39, which display its close relation with Tregs [7,8,9], Th17 cells [10, 11], γδ T cells [12], and Bregs [13]
A variety of molecules are involved in Treg-mediated suppression mechanisms, including IL-2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), glucocorticoid induced tumor necrosis factor receptor (GITR), IL-10, TGF-β, IL-35, LAG3, granzyme B, adenosine, and cyclic adenosine monophosphate (cAMP) [43]
Summary
Extracellular adenosine and ATP exert important functions in physiology and pathophysiology. It is not contradictory that adenosine inhibits the differentiation toward Th17 cells while it promotes differentiation toward Tregs It is regarded as a key endogenous molecule that regulates tissue function by activating four G-protein-coupled P1 receptors, denoted A1, A2A, A2B, and A3 [35]. A variety of molecules are involved in Treg-mediated suppression mechanisms, including IL-2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), glucocorticoid induced tumor necrosis factor receptor (GITR), IL-10, TGF-β, IL-35, LAG3 (lymphocyte-activation gene3), granzyme B, adenosine, and cAMP [43]. Recent researches have shown that CD277 plays a leading role [82] in Vγ9Vδ2 T activation and CD39 on them is an important surface marker [8] Both of mice naïve and induced CD39+ γδ T cells expressed CD25 rather than FOXP3 nor CTLA-4, but have a stronger suppressive function via IL-10 [8].
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