@article{dd5b4cfd64134c4a8af7804d38056a90,
title = "Role of the EHD Family of Endocytic Recycling Regulators for TCR Recycling and T Cell Function",
abstract = "T cells use the endocytic pathway for key cell biological functions, including receptor turnover and maintenance of the immuno-logical synapse. Some of the established players include the Rab GTPases, the SNARE complex proteins, and others, which function together with EPS-15 homology domain-containing (EHD) proteins in non-T cell systems. To date, the role of the EHD protein family in T cell function remains unexplored. We generated conditional EHD1/3/4 knockout mice using CD4-Cre and crossed these with mice bearing a myelin oligodendrocyte glycoprotein-specific TCR transgene. We found that CD4+ T cells from these mice exhibited reduced Ag-driven proliferation and IL-2 secretion in vitro. In vivo, these mice exhibited reduced severity of experimental autoimmune encephalomyelitis. Further analyses showed that recycling of the TCR-CD3 complex was impaired, leading to increased lysosomal targeting and reduced surface levels on CD4+ T cells of EHD1/3/4 knockout mice. Our studies reveal a novel role of the EHD family of endocytic recycling regulatory proteins in TCR-mediated T cell functions.",
author = "Iseka, {Fany M.} and Goetz, {Benjamin T.} and Insha Mushtaq and Wei An and Cypher, {Luke R.} and Bielecki, {Timothy A.} and Tom, {Eric C.} and Priyanka Arya and Sohinee Bhattacharyya and Storck, {Matthew D.} and Semerad, {Craig L.} and Talmadge, {James E.} and Mosley, {R. Lee} and Vimla Band and Hamid Band",
note = "Funding Information: This work was supported by National Institutes of Health Grants CA105489, CA87986, CA99163, and CA116552 (to H.B.), as well as CA105489 (supplement; to F.M.I.), and CA96844 and CA144027 (to V.B.). This work was also supported by Funding Information: Department of Defense Grants W81XWH-07-1-0351 and W81XWH-11-1-0171 (to V.B.), a University of Nebraska System Science Collaborative grant (to H.B.), and an Institutional Development Award from the National Institute of General Medical Sciences under National Institutes of Health Grant P30 GM1063. Support for the University of Nebraska Medical Center Confocal, Flow Cytometry, and other core facilities was from National Cancer Institute Cancer Center Support Grant P30CA036727 to the Fred and Pamela Buffett Cancer Center, as well as from funding by National Institute of General Medical Sciences Grant P30 GM1063 and the Nebraska Research Initiative. Publisher Copyright: Copyright {\textcopyright} 2018 by The American Association of Immunologists, Inc.",
year = "2018",
month = jan,
day = "15",
doi = "10.4049/jimmunol.1601793",
language = "English (US)",
volume = "200",
pages = "483--499",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",
}