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Pediatr Res. 2019 Nov 12. doi: 10.1038/s41390-019-0662-7. [Epub ahead of print]

Increased frequency of regulatory T cells in pediatric inflammatory bowel disease at diagnosis: a compensative role?

Author information

1
Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
2
Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Naples, Italy.
3
Department of Molecular Medicine and Medical Biotechnology, University "Federico II", Naples, Italy.
4
Department of Public Health, University "Federico II", Naples, Italy.
5
Department of Biology, University "Federico II", Naples, Italy.
6
Department of Translational Medical Science (Section of Pediatrics), and European Laboratory for the Investigation of Food-Induced Diseases, University "Federico II", Naples, Italy.
7
Laboratory of Immunology, Endocrinology and Experimental Oncology Institute, National Research Council (IEOS-CNR), Naples, Italy.
8
Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Naples, Italy. c.gianfrani@ibp.cnr.it.
9
Department of Translational Medical Science (Section of Pediatrics), and European Laboratory for the Investigation of Food-Induced Diseases, University "Federico II", Naples, Italy. c.gianfrani@ibp.cnr.it.

Abstract

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.

PMID:
31715619
DOI:
10.1038/s41390-019-0662-7

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