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The secreted form of p28 subunit of interleukin (IL)‐27 inhibits biological functions of IL‐27 and suppresses anti‐allogeneic immune responses
Author(s) -
Shimozato Osamu,
Sato Ayako,
Kawamura Kiyoko,
Chiyo Masako,
Ma Guangyu,
Li Quanhai,
Tagawa Masatoshi
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03088.x
Subject(s) - cytotoxic t cell , biology , immune system , cytokine , microbiology and biotechnology , cd8 , interleukin , interleukin 4 , interleukin 2 , interleukin 12 , immunology , in vitro , biochemistry
Summary Interleukin‐27 (IL‐27) is a new IL‐12‐related heterodimeric cytokine comprising a novel p28 molecule and the Epstein–Barr‐virus‐induced gene 3 (EBI3) molecules. It augments initiation of T helper type 1‐mediated immunity by enhancing the proliferation and cytokine production of T cells. In this study, we examined whether a secreted form of IL‐27 subunits would inhibit IL‐27‐mediated immunological responses. COS‐7 cells transduced with the mouse (m) p28 gene secreted a monomeric mp28 protein; however, those transduced with the mEBI3 gene did not detect a mEBI3 protein in the culture supernatants. The secreted mp28 prevented the IL‐27‐mediated signal transduction and activator of transcription 1 phosphorylation and subsequently inhibited the IL‐27‐mediated intercellular adhesion molecule‐1 induction and interferon‐γ production in CD4 + T cells. We generated mp28‐expressing murine carcinoma Colon 26 cells and inoculated a mixture of the mp28‐ and mIL‐27‐expressing Colon 26 cells into syngeneic BALB/c mice. Simultaneous production of mp28 and mIL‐27 from Colon 26 cells suppressed IL‐27‐mediated anti‐tumour effects in the mice. We examined the p28‐mediated immune suppression by inoculating mp28‐expressing myoblasts into allogeneic mice. Forced production of mp28 suppressed the allogeneic cytotoxic T‐lymphocyte induction and subsequently retarded the graft rejection. Furthermore, production of both mp28 and mp40, which inhibits the functions of IL‐12 and IL‐23, prolonged the graft survival longer than the grafts expressing either mp28 or mp40. We propose that p28 can be a regulatory subunit for IL‐27‐mediated cellular immune responses and a possible therapeutic agent to suppress unfavourable immune responses.