Increased frequency of regulatory T cells in pediatric inflammatory bowel disease at diagnosis: a compensative role?
Adolescent
CD4-Positive T-Lymphocytes
/ cytology
Child
Female
Forkhead Transcription Factors
/ metabolism
Humans
Inflammation
Inflammatory Bowel Diseases
/ blood
Interleukin-10
/ metabolism
Leukocytes, Mononuclear
/ cytology
Male
Osteoprotegerin
/ metabolism
Remission Induction
T-Lymphocytes, Regulatory
/ cytology
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
16
01
2019
accepted:
09
09
2019
revised:
26
07
2019
pubmed:
13
11
2019
medline:
16
6
2021
entrez:
13
11
2019
Statut:
ppublish
Résumé
Regulatory T cells (Tregs) play a critical role in maintaining immune homeostasis. We investigated two main types of Tregs, the CD4+FOXP3+ and IL-10+ Tr1, in pediatric subjects with inflammatory bowel disease (IBD) both at diagnosis and after the clinical remission. Peripheral blood Tregs were analyzed in 16 children with Crohn's disease (CD), 19 with ulcerative colitis (UC), and 14 healthy controls (HC). Two cocktails of fluoresceinated antibodies were used to discriminate between CD4+FOXP3+ and Tr1. We observed in both CD and UC groups a higher frequency of Tr1 at diagnosis compared to controls, which decreased at follow-up compared to diagnosis, in particular in UC. Similarly, in UC patients the percentage of CD4+FOXP3+ Tregs markedly decreased at follow-up compared to the same patients at diagnosis and compared to HC. The expression of CTLA-4 in CD4+FOXP3+ Tregs increased in both groups at clinical remission. This study shows that IBD children present at diagnosis an increased frequency of circulating Tregs, probably as a compensative reaction to tissue inflammation. During the clinical remission, the Treg frequency diminishes, and concomitantly, their activation status increases. Notwithstanding, the high Treg density at diagnosis is not sufficient to counteract the inflammation in the childhood IBD.
Sections du résumé
BACKGROUND
Regulatory T cells (Tregs) play a critical role in maintaining immune homeostasis. We investigated two main types of Tregs, the CD4+FOXP3+ and IL-10+ Tr1, in pediatric subjects with inflammatory bowel disease (IBD) both at diagnosis and after the clinical remission.
METHODS
Peripheral blood Tregs were analyzed in 16 children with Crohn's disease (CD), 19 with ulcerative colitis (UC), and 14 healthy controls (HC). Two cocktails of fluoresceinated antibodies were used to discriminate between CD4+FOXP3+ and Tr1.
RESULTS
We observed in both CD and UC groups a higher frequency of Tr1 at diagnosis compared to controls, which decreased at follow-up compared to diagnosis, in particular in UC. Similarly, in UC patients the percentage of CD4+FOXP3+ Tregs markedly decreased at follow-up compared to the same patients at diagnosis and compared to HC. The expression of CTLA-4 in CD4+FOXP3+ Tregs increased in both groups at clinical remission.
CONCLUSION
This study shows that IBD children present at diagnosis an increased frequency of circulating Tregs, probably as a compensative reaction to tissue inflammation. During the clinical remission, the Treg frequency diminishes, and concomitantly, their activation status increases. Notwithstanding, the high Treg density at diagnosis is not sufficient to counteract the inflammation in the childhood IBD.
Identifiants
pubmed: 31715619
doi: 10.1038/s41390-019-0662-7
pii: 10.1038/s41390-019-0662-7
doi:
Substances chimiques
FOXP3 protein, human
0
Forkhead Transcription Factors
0
IL10 protein, human
0
Osteoprotegerin
0
TNFRSF11B protein, human
0
Interleukin-10
130068-27-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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