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RhoH is required to maintain the integrin LFA-1 in a nonadhesive state on lymphocytes

Nature Immunology volume 5, pages 961–967 (2004)Cite this article

Abstract

Lymphocyte function–associated antigen 1 (LFA-1) is relatively nonadhesive on resting lymphocytes; however, the mechanisms underlying changes in its adhesiveness are poorly understood. In this study, we generated a Jurkat T cell clone, J+hi1.14, that contained low amounts of mRNA for RhoH, a leukocyte-specific inhibitory Rho family member. J+hi1.14 cells expressed constitutively adhesive LFA-1 and the cells bound spontaneously to intracellular adhesion molecules 1, 2 and 3. Reconstitution of RhoH mRNA expression in J+hi1.14 cells reverted the adhesion phenotype to that of wild-type. We obtained similar results using RNA interference in peripheral blood lymphocytes. These data demonstrate that RhoH is required for maintenance of lymphocyte LFA-1 in a nonadhesive state.

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Figure 1: Isolation of constitutively adherent Jurkat clones.
Figure 2: One of the two provirus insertions in Jurkat clone J+hi1.14 is in RHOH.
Figure 3: Blot hybridization analysis of Jurkat clone RNA.
Figure 4: The adhesion of J+hi1.14 cells to ICAM-1–Fc is dependent on LFA-1.
Figure 5: An LFA-1-deficient clone derived from J+hi1.14 fails to bind to ICAM-1.
Figure 6: The adhesion phenotype of J+hi1.14 is reverted by cell fusion.
Figure 7: Transfection with RhoH cDNA reverts the J+hi1.14 phenotype to that of wild-type cells.
Figure 8: RhoH RNA interference in human peripheral blood T cells leads to a constitutively adherent phenotype.

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Acknowledgements

We thank X. Bu for technical assistance. Supported by National Institutes of Health (F32AR08632 to L.K.C., R01DK047636 to B.L. and R01AR47243 to L.B.K.), the Leukemia and Lymphoma Society (B.L.), the Lymphoma Research Foundation (X.L.) and the Arthritis Foundation (P.S.).

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  1. Lisa K Cherry

    Present address: Genzyme Corporation, 1 Mountain Road, Framington, Massachusetts, 01701, USA

  2. Bing Lim

    Present address: Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672

Authors and Affiliations

  1. Division of Rheumatology, Department of Medicine, Immunology and Allergy, Brigham & Women's Hospital, Smith Building room 650, 1 Jimmy Fund Way, Boston, 02115, Massachusetts, USA

    Lisa K Cherry, Pascale Schwab & Lloyd B Klickstein

  2. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, 02215, Massachusetts, USA

    Xiaoyu Li & Bing Lim

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Correspondence to Lloyd B Klickstein.

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Cherry, L., Li, X., Schwab, P. et al. RhoH is required to maintain the integrin LFA-1 in a nonadhesive state on lymphocytes. Nat Immunol 5, 961–967 (2004). https://doi.org/10.1038/ni1103

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