The unique expression profile of human TIPE2 suggests new functions beyond its role in immune regulation.

TIPE2 (tumor necrosis factor-α-induced protein 8-like 2, or TNFAIP8L2) is a newly identified negative regulator of innate and adaptive immunity. TIPE2 deficiency in mice leads to systemic inflammation and TIPE2 down-regulation in humans is associated with autoimmunity. However, the nature of human TIPE2-expressing cells in various tissues has not been characterized due to the lack of suitable antibodies. In the present study, we generated specific rabbit antibodies against human TIPE2 and examined human TIPE2 expression in various tissues by Western blot, flow cytometry, and immunohistochemistry. We found that unlike murine TIPE2 that is preferentially expressed by hematopoietic cells, human TIPE2 was also expressed in a wide variety of non-hematopoietic cell types, including hepatocytes, neurons in brain and brainstem, squamous epithelial cells in esophagus and cervix, transitional epithelial cells in bladder and ureter, and glandular epithelial cells in stomach, colon and appendix. For squamous epithelium, the level of TIPE2 expression increased dramatically in terminally differentiated cells with the proliferating precursor cells completely devoid of TIPE2. The unique expressional profile of human TIPE2 suggests new functions beyond controlling innate and adaptive immunity.