Abstract
Imbalance between regulatory and effector T lymphocytes contributes to loss of immunotolerance and plays a permissive role in the initiation, perpetuation, and progression of chronic inflammatory diseases and autoimmune disorders. Regulatory/effector cell balance is governed by the CD39 ectonucleotidase, the prototype member of the NTPDase family that hydrolyzes ATP and ADP into AMP, subsequently converted into adenosine by CD73. Generation of adenosine impacts T-cell function as it contributes to the mechanism of suppression of Tregs and confers regulatory properties to pathogenic Th17-cells. CD39 cell distribution, mechanism of regulation and impact on inflammatory and regulatory signaling pathways are also discussed here. Innovative therapeutic strategies to boost CD39 levels and activity by either administering soluble ADPases or interfering with CD39 inhibitory signals are reviewed. Restoration of CD39 levels and function has enormous translational and clinical implications and should be regarded as an additional form of treatment to be deployed in the chronic inflammatory setting. The key role of CD39 in immunoregulation in the context of Crohn's disease, one of the most frequent manifestations of inflammatory bowel disease, and autoimmune hepatitis, an autoimmune disorder of the liver, is reviewed and discussed here.
Highlights
After release in the extracellular space, adenosine triphosphate (ATP), a mediator of multiple inflammatory processes, is hydrolyzed to adenosine diphosphate (ADP) and adenosine monophosphate (AMP), subsequently converted into immunosuppressive adenosine
We have recently shown that CD39 co-localizes with lipid raft markers like caveolin 1 and flotillin 2 in LPS-primed macrophages exposed to ATP (Savio et al, 2020)
We showed numerical and functional impairment of CD39+ Tregs that fail to generate adenosine, do not control Th17 cell immunity and are more prone to acquire phenotypic features of effector cells when exposed to a pro-inflammatory challenge (Grant et al, 2014)
Summary
Luiz Eduardo Baggio Savio 1, Simon C. Imbalance between regulatory and effector T lymphocytes contributes to loss of immunotolerance and plays a permissive role in the initiation, perpetuation, and progression of chronic inflammatory diseases and autoimmune disorders. Generation of adenosine impacts T-cell function as it contributes to the mechanism of suppression of Tregs and confers regulatory properties to pathogenic Th17-cells. CD39 cell distribution, mechanism of regulation and impact on inflammatory and regulatory signaling pathways are discussed here. Innovative therapeutic strategies to boost CD39 levels and activity by either administering soluble ADPases or interfering with CD39 inhibitory signals are reviewed. The key role of CD39 in immunoregulation in the context of Crohn’s disease, one of the most frequent manifestations of inflammatory bowel disease, and autoimmune hepatitis, an autoimmune disorder of the liver, is reviewed and discussed here
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
