| First Author | Luan YY | Year | 2011 |
| Journal | Mol Immunol | Volume | 49 |
| Issue | 1-2 | Pages | 219-26 |
| PubMed ID | 21963221 | Mgi Jnum | J:177456 |
| Mgi Id | MGI:5295125 | Doi | 10.1016/j.molimm.2011.08.016 |
| Citation | Luan YY, et al. (2011) Expression of tumor necrosis factor-alpha induced protein 8 like-2 contributes to the immunosuppressive property of CD4(+)CD25(+) regulatory T cells in mice. Mol Immunol 49(1-2):219-26 |
| abstractText | Tumor necrosis factor-alpha induced protein 8 like-2 (TNFAIP8L2, TIPE2), a lately discovered negative regulator of innate immunity and cellular immunity, shares considerable sequence homology with members of the tumor necrosis factor-alpha induced protein 8 (TNFAIP8) family. It is preferentially expressed in lymphoid-derived and marrow-derived cells. However, it is unclear whether TIPE2 is expressed in the regulatory T cells (Tregs) to contribute to its negative regulatory property in immune response. The present study was designed to examine whether naturally occurring CD4(+)CD25(+) Tregs isolated from murine spleens expressed TIPE2 by the use of Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Based on the expression of cell surface molecules, including cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix transcription factor p3 (Foxp3) on CD4(+)CD25(+) Tregs, and cytokines including interleukin (IL)-10 as well as transforming growth factor (TGF)-beta were analyzed to investigate the functional role of TIPE2 in controlling suppressive activity of CD4(+)CD25(+) Tregs. Meanwhile, IL-2, the ratio of interferon (IFN)-gamma/IL-4 in CD4(+)CD25(+)Treg/CD4(+)CD25(-) T cell coculture supernatant and nuclear factor of activated T cells (NF-AT) activation in T lymphocytes were determined to examine the effects of TIPE2 on the T-cell proliferation and differentiation induced by CD4(+)CD25(+) Tregs. It was found that TIPE2 was a cytoplasmic protein expressed in CD4(+)CD25(+) Tregs, and cell surface molecules as well as cytokines (IL-10, TGF-beta) expressions were significantly down-regulated when TIPE2 gene silenced by siRNA. On the other hand, CD4(+)CD25(+) Tregs treated with TIPE2 knock-down promoted T-cell proliferation as well as differentiation, and markedly upregulated IL-2 expression and intranuclear NF-AT activation. The results suggested that TIPE2 appeared to be a critical immunoregulatory molecule involved in immunosuppressive function of CD4(+)CD25(+) Tregs. |
