{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:04:04Z","timestamp":1789380244656,"version":"build-2803163510"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In T lymphocytes, Ca2+ release\u2013activated 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\u201313 \u03bcm\/min and B cells at 6 \u03bcm\/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\u2013mediated Ca2+ influx for T cell homing to LNs mediated by high-affinity integrin activation and chemokine-induced transendothelial migration.<\/jats:p>","DOI":"10.4049\/jimmunol.1202212","type":"journal-article","created":{"date-parts":[[2013,3,2]],"date-time":"2013-03-02T10:23:49Z","timestamp":1362219829000},"page":"3197-3206","source":"Crossref","is-referenced-by-count":26,"title":["Orai1 Function Is Essential for T Cell Homing to Lymph Nodes"],"prefix":"10.1093","volume":"190","author":[{"given":"Milton L","family":"Greenberg","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, University of California Irvine , Irvine, CA 92697"},{"name":"Institute for Immunology, University of California Irvine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of California Irvine , Irvine, CA 92697"},{"name":"Institute for Immunology, University of California Irvine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Leverrier","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of California Irvine , Irvine, CA 92697"},{"name":"Institute for Immunology, University of California Irvine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenyuan L","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of California Irvine , Irvine, CA 92697"},{"name":"Institute for Immunology, University of California Irvine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of California Irvine , Irvine, CA 92697"},{"name":"Department of Neurobiology and Behavior, University of California Irvine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Cahalan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of California Irvine , Irvine, CA 92697"},{"name":"Institute for Immunology, University of California Irvine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,4,1]]},"reference":[{"key":"2025032406494987300_r1","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/nri2152","article-title":"Calcium signalling in lymphocyte activation and disease","volume":"7","author":"Feske","year":"2007","journal-title":"Nat. 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