Exacerbation of delayed-type hypersensitivity responses in EBV-induced gene-3 (EBI-3)-deficient mice.
Epstein-Barr virus-induced gene-3 (EBI-3) associates with p28 to form interleukin-27 (IL-27) or with IL-12p35 to form IL-35. Both IL-27 and IL-35 have immunosuppressive functions and especially IL-35 has been implicated in the suppressive function of regulatory T cells (Treg). To address the role of EBI-3 in immune regulation, delayed-type hypersensitivity (DTH) responses were examined in EBI-3-deficient (EBI-3(-/-)) mice. EBI-3(-/-) mice developed deteriorated DTH responses as shown by the enhanced footpad swelling and augmented infiltration of inflammatory cells into the antigen-challenged footpads as compared with wild-type (WT) mice. While EBI-3-deficiency showed little effects on antigen-specific IFN-gamma production of lymph node cells, IL-17 production was drastically augmented in EBI-3(-/-) cells as compared with in WT cells. In addition, reduced IL-10 production was also evident in EBI-3(-/-) CD4(+) T cells. Interestingly, the development and suppressive function of Treg to inhibit effector T cell proliferation was not affected by EBI-3-deficiency. These data clearly demonstrated the immunosuppressive function of EBI-3 and provided complementary evidence that EBI-3 and EBI-3-containing cytokines might be taken into consideration as potential targets for some immune-related diseases.
Tong
Honglian
H
Department of Pharmacy, FuZhou Medical College of NanChang University, FuZhou 344000, China.
Miyazaki
Yoshiyuki
Y
Yamazaki
Masanori
M
Hara
Hiromitsu
H
Waldmann
Herman
H
Hori
Shohei
S
Yoshida
Hiroki
H
D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005528:Foot / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D007165:Immunosuppression Therapy; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D016207:Cytokines; C499601:Ebi3 protein, mouse; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine