| First Author | Sun H | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 6617 |
| PubMed ID | 32313148 | Mgi Jnum | J:297874 |
| Mgi Id | MGI:6479357 | Doi | 10.1038/s41598-020-63629-w |
| Citation | Sun H, et al. (2020) The TIPE Molecular Pilot That Directs Lymphocyte Migration in Health and Inflammation. Sci Rep 10(1):6617 |
| abstractText | Lymphocytes are some of the most motile cells of vertebrates, constantly navigating through various organ systems. Their specific positioning in the body is delicately controlled by site-specific directional cues such as chemokines. While it has long been suspected that an intrinsic molecular pilot, akin to a ship's pilot, guides lymphocyte navigation, the nature of this pilot is unknown. Here we show that the TIPE (TNF-alpha-induced protein 8-like) family of proteins pilot lymphocytes by steering them toward chemokines. TIPE proteins are carriers of lipid second messengers. They mediate chemokine-induced local generation of phosphoinositide second messengers, but inhibit global activation of the small GTPase Rac. TIPE-deficient T lymphocytes are completely pilot-less: they are unable to migrate toward chemokines despite their normal ability to move randomly. As a consequence, TIPE-deficient mice have a marked defect in positioning their T lymphocytes to various tissues, both at the steady-state and during inflammation. Thus, TIPE proteins pilot lymphocytes during migration and may be targeted for the treatment of lymphocyte-related disorders. |
