Article abstract
Nature Immunology 10, 185 - 194 (2009)
Published online: 11 January 2009 | doi:10.1038/ni.1691
Regulation of conformer-specific activation of the integrin LFA-1 by a chemokine-triggered Rho signaling module
Matteo Bolomini-Vittori1, Alessio Montresor1,2, Cinzia Giagulli1,2, Donald Staunton3, Barbara Rossi1, Marianna Martinello1, Gabriela Constantin1 & Carlo Laudanna1,2
Abstract
Regulation of the affinity of the 
2 integrin LFA-1 by chemokines is critical to lymphocyte trafficking, but the signaling mechanisms that control this process are not well understood. Here we investigated the signaling events controlling LFA-1 affinity triggering by chemokines in human primary T lymphocytes. We found that the small GTPase Rac1 mediated chemokine-induced LFA-1 affinity triggering and lymphocyte arrest in high endothelial venules. Unexpectedly, another Rho family member, Cdc42, negatively regulated LFA-1 activation. The Rho effectors PLD1 and PIP5KC were also critical to LFA-1 affinity modulation. Notably, PIP5KC was found to specifically control the transition of LFA-1 from an extended low–intermediate state to a high-affinity state, which correlated with lymphocyte arrest. Thus, chemokines control lymphocyte trafficking by triggering a Rho-dependent signaling cascade leading to conformer-specific modulation of LFA-1 affinity
- University of Verona, School of Medicine, Department of Pathology, Division of General Pathology, Verona 37134, Italy.
- The Center for Biomedical Computing, University of Verona, Verona 37134, Italy.
- ICOS, Bothell, Washington 98021, USA.
Correspondence to: Carlo Laudanna1,2 e-mail: carlo.laudanna@univr.it
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