TY - JOUR
T1 - Exacerbation of delayed-type hypersensitivity responses in EBV-induced gene-3 (EBI-3)-deficient mice
AU - Tong, Honglian
AU - Miyazaki, Yoshiyuki
AU - Yamazaki, Masanori
AU - Hara, Hiromitsu
AU - Waldmann, Herman
AU - Hori, Shohei
AU - Yoshida, Hiroki
N1 - Funding Information:
The authors thank Ms. Baba and Takao for animal husbandry, and Ms. Furukawa for secretarial support. This work was in part supported by grants from the Ministry of Education, Science, Technology, Sports and Culture of Japan ( KAKENHI 21790474 (Y.M.). and 21022038 (H.Y.) ). This work was also supported by Grant-in-Aid of the Japan Medical Association (H.Y.).
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/2
Y1 - 2010/2
N2 - 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-γ 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.
AB - 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-γ 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.
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U2 - 10.1016/j.imlet.2010.01.001
DO - 10.1016/j.imlet.2010.01.001
M3 - Article
C2 - 20064562
AN - SCOPUS:77249097317
VL - 128
SP - 108
EP - 115
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
IS - 2
ER -