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Competitive Homing Assays to Study Gut-tropic T Cell Migration
Published on: March 1, 2011
Orai1 function is essential for T cell homing to lymph nodes
Milton L Greenberg1, Ying Yu, Sabrina Leverrier
1Department of Physiology and Biophysics, University of California Irvine, Irvine, CA 92697, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 5, 2013
Summary
Calcium-release-activated calcium (CRAC) channels are essential for T cell homing to lymph nodes. Inhibiting CRAC channels blocks T cell migration by preventing integrin activation and chemokine-induced transendothelial movement.
Area of Science:
- Immunology
- Cell Biology
- Physiology
Background:
- Calcium-release-activated calcium (CRAC) channels, formed by Orai1 subunits, are crucial for T lymphocyte activation via the NFAT pathway.
- Understanding lymphocyte homing mechanisms is vital for immune response and therapeutic strategies.
Purpose of the Study:
- To investigate the role of CRAC channel function in lymphocyte homing and migration.
- To determine if suppressing CRAC channel activity impacts T and B lymphocyte homing to lymph nodes.
Main Methods:
- Utilized a dominant-negative Orai1-E106A mutant to inhibit CRAC channel function in human and mouse T cells.
- Transferred human lymphocytes into immunocompromised NOD.SCID mice to assess homing and migration within lymph nodes.
- Employed two-photon microscopy to track lymphocyte movement within lymph nodes.
Main Results:
- Human T and B lymphocytes successfully homed and migrated within murine lymph nodes, similar to endogenous lymphocytes.
- Inhibition of CRAC channels with Orai1-E106A prevented T cell homing into lymph nodes and impaired CCL21-induced calcium signaling.
- CRAC channel inhibition disrupted high-affinity integrin LFA-1 activation, hindering T cell transendothelial migration.
Conclusions:
- CRAC channel-mediated calcium influx is essential for T cell homing to lymph nodes.
- High-affinity integrin activation and chemokine-induced transendothelial migration are dependent on CRAC channel function.
- Targeting CRAC channels represents a potential strategy to modulate lymphocyte trafficking in immune responses.
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