IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis
J. Clin. Invest. Ken Sugimoto, et al. 118:534 doi:10.1172/JCI33194 [
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Figure 3Rapid attenuation of colitis by local IL-22 gene delivery. (
A and
B) Complexes of IL-22 secretion or mock vector with DOTAP/enhancer reagent were microinjected into the proximal part of colon of TCRαKO mice with colitis. Expressions of IL-22 in the noninjected distal part and injected proximal part are shown in
A. Results represent the averages ± SEM (
n = 6–7). **
P < 0.005. Protein lysates from the CECs of the proximal part of colon with mock or IL-22 gene delivery were subjected to immunoblot for evaluation of STAT3 activation (
B). (
C–
H) Laparotomy was carried out on anesthetized TCRαKO mice (24 weeks of age) to confirm the presence of severe colitis as indicated by a marked enlargement of colonic diameter (before injection). Local gene delivery of IL-22 or mock vector into the proximal part (just below the ileocecal junction) was performed in selected TCRαKO mice (
n = 7 each group) that had severe colitis. Mice were sacrificed 2 weeks after microinjection. IL-22 gene delivery attenuated the inflammation at the injection sites; colonic diameter at the injection sites was markedly reduced in TCRαKO mice that received IL-22 (
C, right panels) but not mock (
C, left panels) vector delivery. Results are summarized in
D. Colonic thickness (
E) and disease score (
F), which were evaluated by histological examination (
n = 6–7), are shown. Histology of the proximal colon where gene delivery with mock (left panel) or IL-22 vector (right panel) was received are shown in
G. Original magnification, ×10. (
H) Percentages of goblet cells among total epithelial cells within the colon where mock (
n = 6) or IL-22 (
n = 6) vector delivery were received are shown. *
P < 0.001.