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.
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Acknowledgements
Authors would like to thank all of the young participants in the study. G.M. was supported by grants from European Research Council Grant “menTORingTregs” n.310496, Fondazione Italiana Sclerosi Multipla (FISM) n.2016/R/18, and Telethon n.GGP17086.
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A.V., C.S., and S.V. contributed to conception and design of the study, sample collection, analysis and interpretation of data, and drafted the article; M.S., E.S., and E.M. contributed to patient enrolment and analysis, and interpretation of data; D.B. contributed to analysis and interpretation of data; A.S. and R.T. revised the article critically for important intellectual content; G.M. and C.G. contributed to conception, design and intellectual content of the study, revised the data, and drafted the article.
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The authors declare no competing interests and no funding to disclose with regard to this paper; A.S. served as investigator and member of advisory board for the following companies: D.M.G, Valeas, Angelini, Miltè, Danone, Nestlé, Sucampo, Menarini. E.M. served as investigator and member of advisory board for the following companies: Abbvie, Angelini, Bioprojet, Ferring, Menarini, Milte, Valeas; G.M. served as investigator and member of advisory board for the following companies: Merck, Biogen, Novartis, Aegerion. C.G. served as investigator and member of advisory board for Nemysis.
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Vitale, A., Strisciuglio, C., Vitale, S. et al. Increased frequency of regulatory T cells in pediatric inflammatory bowel disease at diagnosis: a compensative role?. Pediatr Res 87, 853–861 (2020). https://doi.org/10.1038/s41390-019-0662-7
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DOI: https://doi.org/10.1038/s41390-019-0662-7
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