Orai1 Function Is Essential for T Cell Homing to Lymph Nodes
| Autor: | Sabrina Leverrier, Shenyuan L. Zhang, Ying Yu, Milton L. Greenberg, Michael D. Cahalan, Ian Parker |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
ORAI1 Protein
T-Lymphocytes T cell Immunology High endothelial venules Mice SCID Biology Article Immunocompromised Host Mice Cell Movement Mice Inbred NOD Medicine and Health Sciences Lymph node stromal cell medicine Animals Humans Immunology and Allergy Calcium Signaling Lymphocyte function-associated antigen 1 Lymphocyte homing receptor Chemokine CCL21 Lymphocyte Function-Associated Antigen-1 Gut-specific homing Cell biology medicine.anatomical_structure Cell Tracking Mutation Calcium Channels Lymph Nodes Lymph Homing (hematopoietic) |
| Zdroj: | Greenberg, Milton L.; Yu, Ying; Leverrier, Sabrina; Zhang, Shenyuan L.; Parker, Ian; & Cahalan, Michael D.(2013). Orai1 Function is Essential for T Cell Homing to Lymph Nodes. Journal of immunology (Baltimore, Md. : 1950), 190(7), 3197-3206. UC Irvine: Institute for Clinical and Translational Science. Retrieved from: http://www.escholarship.org/uc/item/5mq7x28r |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | In T lymphocytes, Ca2+ release–activated Ca2+ (CRAC) channels composed of Orai1 subunits trigger Ag-induced gene expression and cell proliferation through the NFAT pathway. We evaluated the requirement of CRAC channel function for lymphocyte homing using expression of a dominant-negative Orai1-E106A mutant to suppress Ca2+ signaling. To investigate homing and motility of human lymphocytes in immunocompromised mouse hosts, we transferred human lymphocytes either acutely or after stable engraftment after a second transfer from the same blood donor. Human and mouse lymphocyte homing was assessed, and cells were tracked within lymph nodes (LNs) by two-photon microscopy. Our results demonstrate that human T and B lymphocytes home into and migrate within the LNs of immunocompromised NOD.SCID mice similar to murine lymphocytes. Human T and B cells colocalized in atrophied or reconstituted mouse LNs, where T cells migrated in a random walk at velocities of 9–13 μm/min and B cells at 6 μm/min. Expression of Orai1-E106A inhibited CRAC channel function in human and mouse T cells, and prevented homing from high endothelial venules into murine LNs. 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 LNs mediated by high-affinity integrin activation and chemokine-induced transendothelial migration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|