BACKGROUND: Inflammatory bowel disease (IBD) of pediatric and adult onset differs in several aspects although little knowledge exists about pathogenic disparity. Regulatory T cells (Tregs) characterized as CD4+CD25+Foxp3+ are modulators of gut homeostasis, but their role in human IBD remains unclear. OBJECTIVE: To evaluate the mucosal distribution of Foxp3+ and CD25+ cells in untreated pediatric IBD patients at the time of diagnosis. MATERIAL AND METHODS: Untreated pediatric (n = 14) and adult (n = 12) Crohn's disease (CD) patients were prospectively included together with age-matched symptomatic controls. Colonic and ileal mucosal biopsies collected at diagnosis were studied by immunohistochemistry for enumeration of T cells and for mucosal expression of Foxp3 and CD25. Multicolor immunofluorescence staining was performed in situ to phenotype Foxp3+ cells as Tregs and characterize the CD25+ cells. RESULTS: The density of mucosal T cells displayed only small variations, while that of Foxp3+ cells and CD25+ cells was increased in CD patients. Multicolor immunofluorescence showed that most CD25+ cells were macrophages. Interestingly, in the ileum of pediatric CD patients the density of Foxp3+ cells was significantly higher than in adult CD patients. Co-expression of Foxp3 and CD25, as well as Foxp3 and CTLA-4, indicated that the Foxp3+ cells were Tregs. CONCLUSION: Mucosal numbers of Foxp3(+) Tregs and activated (CD25+) macrophages are elevated in both pediatric and adult ileal CD. The greater increase of ileal Foxp3+ Tregs in pediatric CD than in adult CD might contribute to the relatively less frequent phenotype of isolated ileal enteritis in CD children.
BACKGROUND:Inflammatory bowel disease (IBD) of pediatric and adult onset differs in several aspects although little knowledge exists about pathogenic disparity. Regulatory T cells (Tregs) characterized as CD4+CD25+Foxp3+ are modulators of gut homeostasis, but their role in human IBD remains unclear. OBJECTIVE: To evaluate the mucosal distribution of Foxp3+ and CD25+ cells in untreated pediatric IBD patients at the time of diagnosis. MATERIAL AND METHODS: Untreated pediatric (n = 14) and adult (n = 12) Crohn's disease (CD) patients were prospectively included together with age-matched symptomatic controls. Colonic and ileal mucosal biopsies collected at diagnosis were studied by immunohistochemistry for enumeration of T cells and for mucosal expression of Foxp3 and CD25. Multicolor immunofluorescence staining was performed in situ to phenotype Foxp3+ cells as Tregs and characterize the CD25+ cells. RESULTS: The density of mucosal T cells displayed only small variations, while that of Foxp3+ cells and CD25+ cells was increased in CD patients. Multicolor immunofluorescence showed that most CD25+ cells were macrophages. Interestingly, in the ileum of pediatric CD patients the density of Foxp3+ cells was significantly higher than in adult CD patients. Co-expression of Foxp3 and CD25, as well as Foxp3 and CTLA-4, indicated that the Foxp3+ cells were Tregs. CONCLUSION: Mucosal numbers of Foxp3(+) Tregs and activated (CD25+) macrophages are elevated in both pediatric and adult ileal CD. The greater increase of ileal Foxp3+ Tregs in pediatric CD than in adult CD might contribute to the relatively less frequent phenotype of isolated ileal enteritis in CD children.
Authors: Helioswilton Sales-Campos; Patrícia R de Souza; Paulo J Basso; Viviani Nardini; Angelica Silva; Fernanda Banquieri; Vanessa B F Alves; Javier E L Chica; Auro Nomizo; Cristina R B Cardoso Journal: Immunology Date: 2016-10-07 Impact factor: 7.397
Authors: James B Canavan; Cristiano Scottà; Anna Vossenkämper; Rimma Goldberg; Matthew J Elder; Irit Shoval; Ellen Marks; Emilie Stolarczyk; Jonathan W Lo; Nick Powell; Henrieta Fazekasova; Peter M Irving; Jeremy D Sanderson; Jane K Howard; Simcha Yagel; Behdad Afzali; Thomas T MacDonald; Maria P Hernandez-Fuentes; Nahum Y Shpigel; Giovanna Lombardi; Graham M Lord Journal: Gut Date: 2015-02-24 Impact factor: 23.059
Authors: Urko M Marigorta; Lee A Denson; Jeffrey S Hyams; Kajari Mondal; Jarod Prince; Thomas D Walters; Anne Griffiths; Joshua D Noe; Wallace V Crandall; Joel R Rosh; David R Mack; Richard Kellermayer; Melvin B Heyman; Susan S Baker; Michael C Stephens; Robert N Baldassano; James F Markowitz; Mi-Ok Kim; Marla C Dubinsky; Judy Cho; Bruce J Aronow; Subra Kugathasan; Greg Gibson Journal: Nat Genet Date: 2017-08-14 Impact factor: 38.330