CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses.
We have previously found that CD30 ligand (CD30L; CD153)/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production. In this study, we investigated the role of CD30L in the development of colitis experimentally induced by dextran sulfate sodium (DSS), in which IL-17A is involved in the pathogenesis. CD30L(-/-) mice were resistant to both acute colitis induced by administration of 3 to ∼ 5% DSS and to chronic colitis induced by administration of 1.5% DSS on days 0-5, 10-15, and 20-25 as assessed by weight loss, survival rate, and histopathology. The levels of IFN-γ, IL-17A, and IL-10 were significantly lower but the IL-2 level higher in the lamina propria T lymphocytes of CD30L(-/-) mice than those in lamina propria T lymphocytes of wild-type mice after DSS administration. Soluble murine CD30-Ig fusion protein, which was capable of inhibiting Th17 cell differentiation in vitro, ameliorated both types of DSS-induced colitis in wild-type mice. Modulation of CD30L/CD30 signaling by soluble CD30 could be a novel biological therapy for inflammatory diseases associated with Th17 responses.
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Xun
X
Sun
Hisakata
H
Yamada
Kensuke
K
Shibata
Hiromi
H
Muta
Kenzaburo
K
Tani
Eckhard R
ER
Podack
Yoichiro
Y
Iwakura
Yasunobu
Y
Yoshikai
D000208:Acute Disease; D000818:Animals; D053285:CD30 Ligand / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D017730:Ki-1 Antigen / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
D053285:CD30 Ligand; D016207:Cytokines; D007136:Immunoglobulins; D017730:Ki-1 Antigen; D011993:Recombinant Fusion Proteins; C505775:Tnfsf8 protein, mouse; D016264:Dextran Sulfate