title: Expression of tumor necrosis factor-α induced protein 8 like-2 contributes to the immunosuppressive property of CD4(+)CD25(+) regulatory T cells in mice.
abstract: Tumor necrosis factor-α 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-α 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)-β 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)-γ/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-β) 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.
authors.affiliation: Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, People's Republic of China.
authors.forename: Ying-yi
authors.initials: YY
authors.lastname: Luan
authors.forename: Yong-ming
authors.initials: YM
authors.lastname: Yao
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.forename: Qing-hong
authors.initials: QH
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Sheng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D007108:Immune Tolerance / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C529002:TIPE2 protein, mouse