Instituto de Biomedicina de Sevilla, IBiS (Universidad de Sevilla, HUVR, Junta de Andalucía, CSIC), Seville, Spain
Peripheral CD39-expressing T regulatory cells are increased and associated with relapsing-remitting multiple sclerosis in relapsing patients.
CD39, an ectonucleotidase that hydrolyses pro-inflammatory ATP, is a marker of highly active and suppressive T regulatory cells (Tregs). Although CD39 has a role in Treg suppression and might be important in the control of neuroinflammation in relapsing-remitting multiple sclerosis (RR-MS), to date, there are contradictory reports concerning the Tregs expression of CD39 in RR-MS patients. Thus, our objectives were to assess the activity and expression of CD39, especially in Tregs from peripheral blood mononuclear cells (PBMCs) of relapsing RR-MS patients compared with control subjects and to evaluate the association of CD39+ Tregs with disability and the odds of RR-MS. The activity and expression of CD39 and the CD39+ Treg frequency were measured in PBMCs from 55 relapsing RR-MS patients (19 untreated and 36 receiving immunomodulatory treatment) and 55 age- and sex-paired controls. Moreover, the association between CD39+ Tregs and RR-MS was assessed by multivariate logistic regression. CD39 activity and the frequency of CD39-expressing Tregs were elevated in relapsing RR-MS patients. Moreover, CD39+ Tregs were significantly correlated with the EDSS score and were independently associated with the odds of RR-MS. Our results highlight the relevance of CD39+ Treg subset in the clinical outcomes of RR-MS.
Institute of Immunology and Molecular Medicine, Jining Medical University, China
Implications of CD39 in immune-related diseases
Extracellular adenosine triphosphate (eATP) mediates pro-inflammatory responses by recruiting and activating inflammatory cells. CD39 can hydrolyze eATP into adenosine monophosphate (AMP), while CD73 can convert AMP into the immunosuppressive nucleoside adenosine (ADO). CD39 is a rate-limiting enzyme in this cascade, which is regarded as an immunological switch shifting the ATP-mediated pro-inflammatory environment to the ADO- mediated anti-inflammatory status. The CD39 expression can be detected in a wide spectrum of immunocytes, which is under the influence of environmental and genetic factors. It is increasingly suggested that, CD39 participates in some pathophysiological processes, like inflammatory bowel disease (IBD), sepsis, multiple sclerosis (MS), allergic diseases, ischemia-reperfusion (I/R) injury, systemic lupus erythematosus (SLE), diabetes and cancer. Here, we focus on the current understanding of CD39 in immunity, and comprehensively illustrate the diverse CD39 functions within a variety of disorders.