Histopathological Features of Inflammatory Bowel Disease are Associated With Different CD4+ T Cell Subsets in Colonic Mucosal Lamina Propria

J Crohns Colitis. 2018 Nov 28;12(12):1448-1458. doi: 10.1093/ecco-jcc/jjy116.

Abstract

Background: Inflammatory bowel disease [IBD] results particularly from an aberrance of CD4+ helper and regulatory T cells and comprises histopathologically chronic active enterocolitis with features reflecting both activity and chronicity of mucosal inflammation. The exact immunological-histological correlation in IBD is not understood.

Methods: We studied the correlation between colonic mucosal CD4+ T cell subsets [Th1, Th2, Th17, Th22 and Treg] and mucosal histological changes in ulcerative colitis [UC] and Crohn's disease [CD]. CD4+ T cell subtyping and enumeration were achieved by flow cytometry. Histological features were categorized and assessed semi-quantitatively using three validated histological scoring schemes [ECAP, RHI and D'Haens]. Correlations between prevalence [%] of CD4+ T cell subsets and histological scores were analysed.

Results: Treg cells were correlated with ECAP category A [activity] as well as RHI scores. Treg cell were increased particularly in mucosa with severe neutrophilic infiltration in the cryptal/surface epithelium and in lamina propria, and with basal plasmacytosis. Th17 cells were also increased in cases with extensive neutrophil infiltrate in lamina propria, whereas RORc+ cells were increased in cases with severe lymphoplasmacytic infiltration in lamina propria. In both UC and CD, mucosa with marked crypt architectural alteration had increased IL-22+ and Th22 cells. UC with Paneth cell metaplasia had higher Th17 cells. CD with granuloma had increased IL-22+ and IL-22+IFN-γ+ cells.

Conclusions: The Treg subset appears to be associated with the overall severity of IBD histopathology, particularly with active inflammation. Th17 is also associated with activity. By contrast, IL-22+ cells are associated with chronicity and granuloma formation in CD.

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • Colitis, Ulcerative* / immunology
  • Colitis, Ulcerative* / pathology
  • Crohn Disease* / immunology
  • Crohn Disease* / pathology
  • Disease Progression
  • Female
  • Granuloma / etiology
  • Granuloma / immunology
  • Granuloma / pathology
  • Humans
  • Inflammation / pathology
  • Intestinal Mucosa* / immunology
  • Intestinal Mucosa* / pathology
  • Male
  • Middle Aged
  • Neutrophil Infiltration
  • Patient Acuity
  • Severity of Illness Index
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / pathology
  • Th17 Cells / immunology
  • Th17 Cells / pathology*