MAIT cells exacerbate the disease course of oxazolone-induced colitis. (#167)
Background: Ulcerative colitis (UC) is a chronic, relapsing-remitting, inflammatory disorder of the large intestine in humans. Previously, we have reported that mucosal associated invariant T (MAIT) cells were activated in the peripheral blood and accumulated in the inflamed mucosa in the patients with UC. This study aimed at investigating the role of these cells in the pathogenesis of oxazolone-induced colitis, a murine model of UC.
Methods: Oxazolone colitis was induced in MR1-/- mice with C57BL/6 background and its littermate MR1+/+controls. Mice were presensitized by application of 3% oxazolone in 100% ethanol to the shaved skin. Five days later, 1% oxazolone solution in 50% ethanol was administered intra-rectally. Mice were examined daily for body weight, stool consistency, hematochezia, and rectal bleeding, and the disease activity index (DAI) were scored by using these parameters. On day 9, mice were euthanized to assess colon length and histology. The severity of colitis was assessed by using histological injury score (Kennedy RJ et al., Br J Surg. 2000).
Results: Even though both MR1-/- and MR1+/+ mice developed colitis, MR1-/- mice exhibited higher survival rate and lower DAI score compared to MR1+/+ mice. The colon length was reduced in MR1+/+ mice. The histological injury score was lower in MR1-/- mice compared to that of MR1+/+mice.
Conclusions: MR1-/- mice developed less severe colitis clinically and histologically compared to MR1+/+ mice. These findings indicate that MAIT cells exacerbate the disease course of oxazolone colitis. Together with previous studies of UC patients by our and other groups, MAIT cells may be playing an important role in inflammatory bowel diseases especially UC.