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- W4313386697 abstract "Abstract In T lymphocytes, Ca2+ release-activated Ca2+ (CRAC) channels composed of Orai1 subunits trigger antigen-induced gene expression through the NFAT pathway. Lymphocyte homing into lymph nodes may also require CRAC channel function. We evaluated the requirements for human lymphocyte homing, using expression of a dominant-negative Orai1-E106A mutant to suppress Ca2+ signaling. To investigate homing and motility of human lymphocytes we transferred human T cells into immunocompromised mouse hosts following stable reconstitution. Human lymphocyte homing was assessed by flow cytometry, and cells were tracked within lymph nodes by two-photon microscopy. Our results demonstrate that human T lymphocytes home into and migrate within the lymph nodes of immunocompromised NOD.SCID.B2 mice, similar to murine lymphocytes. Human T cells migrated in a random walk at velocities of 12.8 ± 0.4 µm/min. Expression of Orai1-E106A inhibited CRAC channel function in human T cells and prevented homing from high endothelial venules into murine lymph nodes. Ca2+ signals induced by CCL21 were also inhibited in T cells expressing Orai1-E106A. With CRAC channels inhibited, the high-affinity form of LFA-1 failed to become active, and T cells failed to migrate across endothelial cells in a transwell model. These results establish a requirement for CRAC channel-mediated Ca2+ influx for T cell homing to lymph nodes mediated by high-affinity integrin activation and chemokine-induced transendothelial migration." @default.
- W4313386697 created "2023-01-06" @default.
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- W4313386697 date "2013-05-01" @default.
- W4313386697 modified "2023-09-27" @default.
- W4313386697 title "Orai1 function is essential for T cell homing to lymph nodes (P5102)" @default.
- W4313386697 doi "https://doi.org/10.4049/jimmunol.190.supp.58.5" @default.
- W4313386697 hasPublicationYear "2013" @default.
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