Type

Journal Article

Authors

Elizabeth J Ryan
Glen A Doherty
Simon C Robson
Alan C Moss
Adam S Cheifetz
Hugh E Mulcahy
Garret Cullen
Theo Rispens
Sean T Martin
Kathryn Byrne
and 5 others

Subjects

Microbiology

Topics
t lymphocytes regulatory animal model multivariate analysis inflammatory bowel disease adoptive transfer tumor necrosis factor t cell flow cytometry

Heightened Expression of CD39 by Regulatory T Lymphocytes Is Associated with Therapeutic Remission in Inflammatory Bowel Disease. (2015)

Abstract To evaluate whether changes in expression of CD39 by regulatory T lymphocytes (Treg) impact treatment response in inflammatory bowel disease. To then define the biological role of expression of CD39 on Treg in an animal model of colitis. A prospective study of consecutive patients commencing anti-tumor necrosis factor therapy with infliximab (IFX) or adalimumab (ADA), who were then followed for 12 months. Treatment responses were defined both symptomatically and by endoscopy showing mucosal healing. Peripheral blood Tregs were quantified by flow cytometry. Functional importance of CD39 expression by Treg was determined in an adoptive T-cell transfer model of colitis. Forty-seven patients (ulcerative colitis, n = 22; Crohn's disease, n = 25) were recruited; 16 patients were complete responders and 13 nonresponders to anti-tumor necrosis factor. CD39 expression by Treg was lower in active inflammatory bowel disease and increased significantly after treatment in responders (CD39Treg/total Treg; 8% at baseline to 22.5% at late time point, P < 0.001). Responders were more likely to have therapeutic drug levels and in multivariate analysis therapeutic drug levels were associated with higher expression of CD39 by FoxP3 Treg and lower frequencies of interleukin 17A expressing cells. Tregs with genetic deletion of CD39 exhibit decrements in potential to suppress intestinal inflammation in a murine (CD45RB) T-cell transfer model of colitis in vivo, when compared with wild-type Treg. Increased expression of CD39 by peripheral blood Treg is observed in the setting of clinical and endoscopic remission in inflammatory bowel disease. Deficiency of CD39 expression by Treg can be linked to inability to suppress experimental colitis.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Elizabeth J Ryan, Glen A Doherty, Simon C Robson, Alan C Moss, Adam S Cheifetz, Hugh E Mulcahy, Garret Cullen, Theo Rispens, Sean T Martin, Kathryn Byrne and 5 others

Experts in our system

1
Elizabeth J Ryan
University College Dublin
 
2
Glen A Doherty
University College Dublin
Total Publications: 57
 
3
Hugh E Mulcahy
University College Dublin
Total Publications: 43
 
4
Garret Cullen
University College Dublin
Total Publications: 17
 
5
Kathryn Byrne
University College Dublin
Total Publications: 16