To Örebro University

Microscopic colitis (MC), divided into lymphocytic colitis (LC) and collagenous colitis (CC), is an inflammatory bowel condition with an unknown cause that commonly afflicts older women. Unlike ulcerative colitis (UC) patients, MC patients have a decreased risk of developing colorectal cancer. The adaptive immune response in MC patients was investigated to elucidate the role of CD8+ T cells.

Luminex analyses were performed in patients with MC, UC and controls. Paper I measured immunomodulatory molecules such as immune checkpoints in serum and colonic biopsies. Paper II examined mediators produced by CD8+ T cells in addition to other chemokines and cytokines in colonic biopsies from MC and UC patients.

In paper I, soluble levels of IDO, PD-1, TIM-3, 4-1BB, CD27 and CD80 were decreased in MC compared to controls, whereas IL-2R∝ and 4-1BBL were increased. In biopsies, increased levels of CTLA-4, PD-1, PD-L1, PD-L2, 4-1BB, APRIL, BAFF and IL-2R∝ were detected whereas levels of TIM-3 and CD27 were decreased in MC patients compared to controls.

In paper II, colonic levels of granzyme B and CCL5 were higher in CC than UC, CCL4 and CD163 were increased at similar levels in CC and UC, and MMP-1, MMP-3 and TNF-RII levels were increased in CC and UC compared to controls. MC and UC patients had increased levels of 4-1BB and perforin. Gp130 and IL-6R∝ were decreased in MC compared to controls.

These studies suggest the presence of an active immunological responsein MC involving CD8+ T cells and different disease mechanismsin MC and UC.