Ricerc@Sapienza

Background and Aims: In ulcerative colitis (UC), inflammation begins in the rectum and
can extend proximally throughout the entire colon. The extension of inflammation is an
important determinant of disease course, and may be limited by the action of regulatory
T cells (Tregs). In this cross-sectional study, we evaluated the relationship between UC
extension and the proportions of CD3+CD4+Foxp3+ and CD3+CD4+LAP+Foxp3-
Tregs in the colonic lamina propria (LP) of 79 UC patients and 29 controls. The role of
these cells in UC extension was also investigated in the murine oxazolone-induced colitis
model.
Methods: Patients: Disease extension was classified according to the Montreal
classification. Where possible, endoscopic biopsies of involved and uninvolved
tissue were obtained from UC patients. Mouse model: Colitis was induced by
intrarectal oxazolone administration. Lamina propria mononuclear cells were isolated
from patient biopsies and mouse colon tissue using enzymatic method and the
percentage of CD3+CD4+Foxp3+ and CD3+CD4+LAP+Foxp3-cells evaluated by
immunofluorescence. Confocal microscopy was applied for the visualization and
quantification of CD4+LAP+ cells on tissue histological sections.
Results: In UC patients with distal colitis the proportion of LP CD3+CD4+Foxp3+
Tregs was significantly higher in inflamed tissue than uninvolved tissue. As opposite, the
proportion of LP CD3+CD4+LAP+ Tregs was significantly higher in uninvolved tissue
than involved tissue. Both LP CD3+CD4+Foxp3+ and LP CD3+CD4+LAP+ Tregs
proportion in involved tissue was significantly higher than in controls irrespective of the
extension of inflammation. In mice with oxazolone-induced distal colitis, treatment with
LAP-depleting antibody was associated with the development of extensive colitis.
Conclusions: Our findings suggest that CD3+CD4+LAP+Foxp3-Tregs limit the
extension of inflammatory lesions in UC patients.