Crossover Subsets of CD4 T Lymphocytes in the Intestinal Lamina Propria of Patients with Crohn's Disease and Ulcerative Colitis.

BACKGROUND

Hovhannisyan et al. first showed evidence of plasticity between Treg and Th17 in the inflamed intestine of Crohn's disease (CD) patients. Our previous report suggests that the inflammatory cytokine milieu generates IL-17 Foxp3 CD4 T lymphocytes which is a crossover population converting Treg subset to Th17 in the peripheral blood of IBD patients. This is considered as an evidence of Treg/Th17 plasticity.

AIM

The aim of this study was to characterize a variety of helper T cell crossover population, not limited to IL-17 Foxp3 CD4 T lymphocytes, in the lamina propria (LP) of IBD patients.

METHODS

Fresh colonoscopic biopsies were obtained from patients with CD (n = 50) and ulcerative colitis (UC, n = 32) and from healthy controls (HC, n = 25). LP mononuclear cells were assessed for intracellular cytokines and transcription factors such as IFNγ, IL-13, IL-17, IL-22, T-bet, Gata-3, RORγt, and Foxp3 using multicolor flow cytometry to detect subsets of LP CD4 T lymphocytes.

RESULTS

Patients with IBD demonstrated increased crossover populations in IL-17 Foxp3, T-bet Foxp3, Gata3 Foxp3, RORγt Foxp3 populations compared to HC. There was an inverse correlation of Harvey-Bradshaw index with Gata3 Foxp3 population in CD patients, while IL-13 Foxp3 population was directly correlated with Mayo clinical scores in UC patients. Furthermore, total IL-22 expressing cells as well as Th22 and IL-22 Th1 populations were decreased in UC compared to CD and HC.

CONCLUSION

IBD patients exhibit the increased crossover populations in LP Treg cells toward Th2 and Th17 compared to HC. The prevalence of Treg/Th2 crossover populations is associated with clinical disease score of IBD.