Tissue-specific Expression of TIPE2 Provides Insights into Its Function

Tumor necrosis factor-alpha-induced protein-8 like-2 (TNFAIP8L2, TIPE2) is a newly discovered negative regulator of innate immunity and cellular immunity. TIPE2 deficiency in mice causes fetal inflammatory diseases and TIPE2 downregulation in humans is associated with systemic autoimmunity. However, TIPE2 deficiency leads to a selective defect in humoral immunity. Due to the lack of a suitable antibody, the nature of cells and tissues that express TIPE2 protein has not been determined. In this study, we generated a highly specific antibody to TIPE2 and examined TIPE2 expression in various murine tissues by immunohistochemistry and RT-PCR. We found that TIPE2 was a cytoplasmic protein expressed preferentially in lymphoid tissues and a small group of non-lymphoid tissues. Within the lymphoid compartment, T cells appear to express high level of TIPE2 protein, while B cells and B cell zones of lymphoid organs were devoid of TIPE2. Within most of the non-lymphoid tissues, TIPE2 was not detected. However, several endocrine tissues and skeletal muscle expressed detectable TIPE2 protein and mRNA. Furthermore, high levels of TIPE2 were detected in monocyte/macrophage derived cell lines and ovarian adenocarcinoma cells, but not detectable or weakly expressed in most human carcinoma cell lines. These results indicate that TIPE2 may perform tissue-specific functions in both lymphoid and non-lymphoid compartments. They may also explain why TIPE2 deficiency enhanced cellular but not humoral immunity.