Update in immune regulatory pathway of tumor necrosis factor-α-induced protein 8-like 2 / 中华危重病急救医学

The tumor necrosis factor-α-induced protein 8-like (TNFAIP8, TIPE) family is recently identified proteins consisting of four highly homologous mammalian proteins: TIPE, TIPE1, TIPE2, and TIPE3. Although the four members share similar molecular structure and function, involving effects in pathophysiological processes of inflammation, immunity, tumors, stroke, angiogenesis, and other diseases, they have individual characteristics. Many studies have shown that TIPE2 is an essential negative regulator of both innate and adaptive immunity. Up-regulation of TIPE2 expression can alleviate excessive inflammation during septic shock and maintain hemostasis of macrophages, neutrophils, dendritic cells, T cells, and B cells. In this review, we summarize the current literature for structure feature, immune function, and regulatory mechanism of TIPE2, together with its clinical significance in the pathogenesis of immune disorders of a wide array of human diseases. Understanding the basic biology of this new molecule might help us to seek novel strategies for the immunomodulation of human diseases.

The potential role and significance of tumor necrosis factor-α induced protein 8 like-2 in autoimmune diseases / 解放军医学杂志

Autoimmune disease is a condition arisen from an abnormal immune response to the tissue cells itself, its precise mechanism remains unknown, and the failure to distinguish self from non-self is often termed a breach of tolerance and is the basis for autoimmune illness. The tumor necrosis factor-α (TNF-α) induced protein 8 like-2 (TIPE2) is a newly discovered member of TNF-α induced protein 8 (TNFAIP8) family which is an essential negative controller of both innate and adaptive immunity. It has been documented that marked expressions of TIPE2 are evident in various autoimmune diseases, including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), myasthenia gravis (MG) and systemic lupus erythematosus (SLE), which appear to be closely related to the severity, progression as well as prognosis of the illness, thereby contribute to the pathogenesis of autoimmune diseases. Deficient expression of TIPE2 might contribute to the hyper-reactivity of auto-reactive lymphocytes and macrophages, or aggregate inflammatory reaction by prompting high concentration of pro-inflammatory cytokines in peripheral blood, thus, trigger the development and progression of autoimmune diseases. In addition, dysregulation of immune homeostasis could be another latent target involved into the mechanism of autoimmune diseases. The present paper summarized the potential role and its mechanism of TIPE2 in the development of autoimmune diseases.

Expression of tumor necrosis factor -α-induced protein -8 -like 2 of bone marrow in children with aplastic anemia and its significance / 中华实用儿科临床杂志

Objective To investigate the characteristics of the bone marrow mesenchymal stem cell(MSC)in children with aplastic anemia(AA)in vitro,and the expressions of tumor necrosis factor -α-induced protein -8 -like 2(TIPE2)in the bone marrow,and the correlation between the level of TIPE2 mRNA with γ-interferon(IFN -γ)and IL -6 in AA patients.Methods Bone marrow samples were collected from 1 8 children with AA(AA group)and 8 children with bone injury (control group)who were hospitalized in Jinan Children′s Hospital from January 201 2 to June 201 5.MSC were isolated and cultured.The morphology of MSC was observed and immune phenotype was detected.The TIPE2 mRNA was detected by using real -time fluorescence quantitative PCR,and the levels of IFN -γand IL -6 were detected by using enzyme linked immunosorbent assay.Results Different sizes had been presented in the primi-tive MSC of AA patients,but the third passage MSC until 80% confluence had manifested the uniform convergence with long spindle and swirl distribution.In the sixth passage,cells showed degenerative change.The primitive and first pa-ssage MSC in patients with AA was longer than that in the controls.CD73 ,CD1 05 ,CD44 and CD90 were expressed in MSC,while CD34 ,CD45 ,CD271 expressed rarely.The level of TIPE2 mRNA in AA patients (5.29 ±1 .56)was obviously lower than that of the control group(8.68 ±2.00),and the difference was significant(t =-4.48,P 0.05).Conclusions The proliferation of MSC is significantly reduced in patients with AA.TIPE2,as an important role to stabilize the immune system,plays an important role in the occurrence of AA by its low expression and up -regula-ting the expression of inflammatory factors.