IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease.
BACKGROUND
A novel T helper (Th) cell lineage, Th17, that exclusively produces the proinflammatory cytokine interleukin 17 (IL17) has been reported to play important roles in various inflammatory diseases. IL23 is also focused upon for its potential to promote Th17. Here, the roles of the IL23/IL17 axis in inflammatory bowel diseases such as ulcerative colitis (UC) and Crohn's disease (CD) were investigated.


METHODS
Mucosal samples were obtained from surgically resected specimens (controls, n = 12; UC, n = 17; CD, n = 22). IL17 production by isolated peripheral blood (PB) and lamina propria (LP) CD4(+) cells was examined. Quantitative PCR amplification was performed to determine the mRNA expression levels of IL17, interferon gamma (IFNgamma), IL23 receptor (IL23R) and retinoic acid-related orphan receptor gamma (RORC) in LP CD4(+) cells, and IL12 family members, such as IL12p40, IL12p35 and IL23p19, in whole mucosal specimens. The effects of exogenous IL23 on IL17 production by LP CD4(+) cells were also examined.


RESULTS
IL17 production was higher in LP CD4(+) cells than in PB. Significant IL17 mRNA upregulation in LP CD4(+) cells was found in UC, while IFNgamma was increased in CD. IL23R and RORC were upregulated in LP CD4(+) cells isolated from both UC and CD. IL17 production was significantly increased by IL23 in LP CD4(+) cells from UC but not CD. Upregulated IL23p19 mRNA expression was correlated with IL17 in UC and IFNgamma in CD.


CONCLUSIONS
IL23 may play important roles in controlling the differential Th1/Th17 balance in both UC and CD, although Th17 cells may exist in both diseases.
Kobayashi
T
T
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Okamoto
S
S
Hisamatsu
T
T
Kamada
N
N
Chinen
H
H
Saito
R
R
Kitazume
M T
MT
Nakazawa
A
A
Sugita
A
A
Koganei
K
K
Isobe
K
K
Hibi
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism*; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000494:pharmacology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
D020381:Interleukin-17; D053759:Interleukin-23