TNFAIP8L2 explained

TNF alpha induced protein 8 like 2 (TNFAIP8L2), also known as TIPE2, is a protein that in humans is encoded by the TNFAIP8L2 gene. It is preferentially expressed in human myeloid cell types and serves as an immune checkpoint regulator of inflammation and metabolism.^[1]

Function

TNFAIP8L2 is a member of the TNFAIP8 (tumor necrosis factor-α-induced protein 8, or TIPE) family that function as transfer proteins for the second messenger lipids PIP2 and PIP3. The other three family members are TNFAIP8, TNFAIP8L1 and TNFAIP8L3.

Structure

The crystal structure of TIPE2 reveals that it contains a large, hydrophobic central cavity that is poised for cofactor binding.^[2]

Clinical significance

TIPE2 acts as a negative regulator of the immune system.^[3] It is down-regulated in patients with infectious and autoimmune diseases and also acts as a tumor suppressor in several types of cancer.^[4] Its knockout leads to leukocytosis and systemic inflammatory disorders in mice.^{[5] [6]}

Notes and References

1. Li T, Wang W, etal . Genome-wide analysis reveals TNFAIP8L2 as an immune checkpoint regulator of inflammation and metabolism . Molecular Immunology . May 2018. 99 . 154–162. 29787979. 10.1016/j.molimm.2018.05.007 . 5995464.
2. Zhang X, Wang J, Fan C, Li H, Sun H, Gong S, Chen YH, Shi Y . Crystal structure of TIPE2 provides insights into immune homeostasis . Nature Structural & Molecular Biology . 16 . 1 . 89–90 . January 2009 . 19079267 . 10.1038/nsmb.1522 . 11111978 .
3. Sun H, Gong S, etal . TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. . Cell . 18455983 . 10.1016/j.cell.2008.03.026 . 2398615 . 2008 . 133 . 3 . 415–26.
4. Li Z, Jia W, Niu J, Zhang L . Understanding the roles of negative immune regulator TIPE2 in different diseases and tumourigenesis . Histology and Histopathology . 33. 919–928 . February 2018 . 9 . 29480508 . 10.14670/HH-11-977 .
5. Goldsmith JR, Chen YH . Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins . Cellular & Molecular Immunology . 14 . 6 . 482–487 . June 2017 . 28287114 . 10.1038/cmi.2017.4 . 5719143 .
6. Lou Y, Liu S . The TIPE (TNFAIP8) family in inflammation, immunity, and cancer . Molecular Immunology . 49 . 1–2 . 4–7 . October 2011 . 21924498 . 10.1016/j.molimm.2011.08.006 .