Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 295 (5562): 2094-2097

Copyright © 2002 by the American Association for the Advancement of Science

Influence of SHIP on the NK Repertoire and Allogeneic Bone Marrow Transplantation

Jia-Wang Wang,1* Julie M. Howson,1* Tomar Ghansah,1* Caroline Desponts,1 John M. Ninos,1 Sarah L. May,1 Kim H. T. Nguyen,1 Noriko Toyama-Sorimachi,2 William G. Kerr1dagger

Natural killer cell (NK) receptors for major histocompatibility complex (MHC) class I influence engraftment and graft-versus-tumor effects after allogeneic bone marrow transplantation. We find that SH2-containing inositol phosphatase (SHIP) influences the repertoire of NK receptors. In adult SHIP-/- mice, the NK compartment is dominated by cells that express two inhibitory receptors capable of binding either self or allogeneic MHC ligands. This promiscuous repertoire has significant functional consequences, because SHIP-/- mice fail to reject fully mismatched allogeneic marrow grafts and show enhanced survival after such transplants. Thus, SHIP plays an important role in two processes that limit the success of allogeneic marrow transplantation: graft rejection and graft-versus-host disease.

1 Immunology Program, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, and Departments of Interdisciplinary Oncology and Biochemistry, University of South Florida, Tampa, FL 33612, USA.
2 Department of Immune Regulation, Tokyo Medical and Dental University, Tokyo 113-8150, Japan.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: kerrw{at}moffitt.usf.edu



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Functional NK Cell Repertoires Are Maintained through IL-2R{alpha} and Fas Ligand.
M. Felices, T. R. Lenvik, D. E. M. Ankarlo, B. Foley, J. Curtsinger, X. Luo, B. R. Blazar, S. K. Anderson, and J. S. Miller (2014)
J. Immunol. 192, 3889-3897
   Abstract »    Full Text »    PDF »
Overexpression of miR-155 causes expansion, arrest in terminal differentiation and functional activation of mouse natural killer cells.
R. Trotta, L. Chen, S. Costinean, S. Josyula, B. L. Mundy-Bosse, D. Ciarlariello, C. Mao, E. L. Briercheck, K. K. McConnell, A. Mishra, et al. (2013)
Blood 121, 3126-3134
   Abstract »    Full Text »    PDF »
Ly49Q Positively Regulates Type I IFN Production by Plasmacytoid Dendritic Cells in an Immunoreceptor Tyrosine-Based Inhibitory Motif-Dependent Manner.
M. M. A. Rahim, L.-H. Tai, A. D. Troke, A. B. Mahmoud, E. Abou-Samra, J. G. Roy, A. Mottashed, N. Ault, C. Corbeil, M.-L. Goulet, et al. (2013)
J. Immunol. 190, 3994-4004
   Abstract »    Full Text »    PDF »
Inositol tetrakisphosphate limits NK cell effector functions by controlling PI3K signaling.
K. Sauer, E. Park, S. Siegemund, A. R. French, J. A. Wahle, L. Sternberg, S. Rigaud, A. H. Jonsson, W. M. Yokoyama, and Y. H. Huang (2013)
Blood 121, 286-297
   Abstract »    Full Text »    PDF »
Quorum Sensing Contributes to Activated IgM-Secreting B Cell Homeostasis.
C. Montaudouin, M. Anson, Y. Hao, S. V. Duncker, T. Fernandez, E. Gaudin, M. Ehrenstein, W. G. Kerr, J.-H. Colle, P. Bruhns, et al. (2013)
J. Immunol. 190, 106-114
   Abstract »    Full Text »    PDF »
Mouse natural killer cell development and maturation are differentially regulated by SHIP-1.
C. Banh, S. M. S. Miah, W. G. Kerr, and L. Brossay (2012)
Blood 120, 4583-4590
   Abstract »    Full Text »    PDF »
Inhibition of PI3K Signaling Spurs New Therapeutic Opportunities in Inflammatory/Autoimmune Diseases and Hematological Malignancies.
J. G. Foster, M. D. Blunt, E. Carter, and S. G. Ward (2012)
Pharmacol. Rev. 64, 1027-1054
   Abstract »    Full Text »    PDF »
An ENU-induced mouse mutant of SHIP1 reveals a critical role of the stem cell isoform for suppression of macrophage activation.
N.-Y. N. Nguyen, M. J. Maxwell, L. M. Ooms, E. M. Davies, A. A. Hilton, J. E. Collinge, D. J. Hilton, B. T. Kile, C. A. Mitchell, M. L. Hibbs, et al. (2011)
Blood 117, 5362-5371
   Abstract »    Full Text »    PDF »
SHIP deficiency causes Crohn's disease-like ileitis.
W. G. Kerr, M.-Y. Park, M. Maubert, and R. W. Engelman (2011)
Gut 60, 177-188
   Abstract »    Full Text »    PDF »
SHIP Represses Th2 Skewing by Inhibiting IL-4 Production from Basophils.
E. Kuroda, F. Antignano, V. W. Ho, M. R. Hughes, J. Ruschmann, V. Lam, T. Kawakami, W. G. Kerr, K. M. McNagny, L. M. Sly, et al. (2011)
J. Immunol. 186, 323-332
   Abstract »    Full Text »    PDF »
SHIP Influences Signals from CD48 and MHC Class I Ligands That Regulate NK Cell Homeostasis, Effector Function, and Repertoire Formation.
N. R. Fortenbery, K. H. T. Paraiso, M. Taniguchi, C. Brooks, L. Ibrahim, and W. G. Kerr (2010)
J. Immunol. 184, 5065-5074
   Abstract »    Full Text »    PDF »
SHIP1 Inhibition Increases Immunoregulatory Capacity and Triggers Apoptosis of Hematopoietic Cancer Cells.
R. Brooks, G. M. Fuhler, S. Iyer, M. J. Smith, M.-Y. Park, K. H. T. Paraiso, R. W. Engelman, and W. G. Kerr (2010)
J. Immunol. 184, 3582-3589
   Abstract »    Full Text »    PDF »
SHIP limits immunoregulatory capacity in the T-cell compartment.
M. M. Collazo, D. Wood, K. H. T. Paraiso, E. Lund, R. W. Engelman, C.-T. Le, D. Stauch, K. Kotsch, and W. G. Kerr (2009)
Blood 113, 2934-2944
   Abstract »    Full Text »    PDF »
SHIP is required for a functional hematopoietic stem cell niche.
A. L. Hazen, M. J. Smith, C. Desponts, O. Winter, K. Moser, and W. G. Kerr (2009)
Blood 113, 2924-2933
   Abstract »    Full Text »    PDF »
The Inositol Phosphatase SHIP Controls Salmonella enterica Serovar Typhimurium Infection In Vivo.
J. L. Bishop, L. M. Sly, G. Krystal, and B. B. Finlay (2008)
Infect. Immun. 76, 2913-2922
   Abstract »    Full Text »    PDF »
Inappropriate Recruitment and Activity by the Src Homology Region 2 Domain-Containing Phosphatase 1 (SHP1) Is Responsible for Receptor Dominance in the SHIP-Deficient NK Cell.
J. A. Wahle, K. H. T. Paraiso, R. D. Kendig, H. R. Lawrence, L. Chen, J. Wu, and W. G. Kerr (2007)
J. Immunol. 179, 8009-8015
   Abstract »    Full Text »    PDF »
The Pten/PI3K pathway governs the homeostasis of V{alpha}14iNKT cells.
H. Kishimoto, T. Ohteki, N. Yajima, K. Kawahara, M. Natsui, S. Kawarasaki, K. Hamada, Y. Horie, Y. Kubo, S. Arase, et al. (2007)
Blood 109, 3316-3324
   Abstract »    Full Text »    PDF »
KLRG1 binds cadherins and preferentially associates with SHIP-1.
M. S. Tessmer, C. Fugere, F. Stevenaert, O. V. Naidenko, H. J. Chong, G. Leclercq, and L. Brossay (2007)
Int. Immunol. 19, 391-400
   Abstract »    Full Text »    PDF »
Induced SHIP Deficiency Expands Myeloid Regulatory Cells and Abrogates Graft-versus-Host Disease.
K. H. T. Paraiso, T. Ghansah, A. Costello, R. W. Engelman, and W. G. Kerr (2007)
J. Immunol. 178, 2893-2900
   Abstract »    Full Text »    PDF »
Ly49B Is Expressed on Multiple Subpopulations of Myeloid Cells.
F. Gays, J. G. Aust, D. M. Reid, J. Falconer, N. Toyama-Sorimachi, P. R. Taylor, and C. G. Brooks (2006)
J. Immunol. 177, 5840-5851
   Abstract »    Full Text »    PDF »
Differential and Nonredundant Roles of Phospholipase C{gamma}2 and Phospholipase C{gamma}1 in the Terminal Maturation of NK Cells.
J. Regunathan, Y. Chen, S. Kutlesa, X. Dai, L. Bai, R. Wen, D. Wang, and S. Malarkannan (2006)
J. Immunol. 177, 5365-5376
   Abstract »    Full Text »    PDF »
Cutting Edge: Dominance by an MHC-Independent Inhibitory Receptor Compromises NK Killing of Complex Targets.
J. A. Wahle, K. H. T. Paraiso, A. L. Costello, E. L. Goll, C. L. Sentman, and W. G. Kerr (2006)
J. Immunol. 176, 7165-7169
   Abstract »    Full Text »    PDF »
SHIP deficiency enhances HSC proliferation and survival but compromises homing and repopulation.
C. Desponts, A. L. Hazen, K. H. T. Paraiso, and W. G. Kerr (2006)
Blood 107, 4338-4345
   Abstract »    Full Text »    PDF »
IFN-{gamma} Acts on T Cells to Induce NK Cell Mobilization and Accumulation in Target Organs.
O. Wald, I. D. Weiss, H. Wald, H. Shoham, Y. Bar-Shavit, K. Beider, E. Galun, L. Weiss, L. Flaishon, I. Shachar, et al. (2006)
J. Immunol. 176, 4716-4729
   Abstract »    Full Text »    PDF »
Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).
B. R. Blazar and W. J. Murphy (2005)
Phil Trans R Soc B 360, 1747-1767
   Abstract »    Full Text »    PDF »
IFN Regulatory Factor-2 Deficiency Revealed a Novel Checkpoint Critical for the Generation of Peripheral NK Cells.
S. Taki, S. Nakajima, E. Ichikawa, T. Saito, and S. Hida (2005)
J. Immunol. 174, 6005-6012
   Abstract »    Full Text »    PDF »
Differential expression of SHIP1 in CD56bright and CD56dim NK cells provides a molecular basis for distinct functional responses to monokine costimulation.
R. Trotta, R. Parihar, J. Yu, B. Becknell, J. Allard II, J. Wen, W. Ding, H. Mao, S. Tridandapani, W. E. Carson, et al. (2005)
Blood 105, 3011-3018
   Abstract »    Full Text »    PDF »
Expansion of Myeloid Suppressor Cells in SHIP-Deficient Mice Represses Allogeneic T Cell Responses.
T. Ghansah, K. H. T. Paraiso, S. Highfill, C. Desponts, S. May, J. K. McIntosh, J.-W. Wang, J. Ninos, J. Brayer, F. Cheng, et al. (2004)
J. Immunol. 173, 7324-7330
   Abstract »    Full Text »    PDF »
Involvement of CXCR4 and IL-2 in the homing and retention of human NK and NK T cells to the bone marrow and spleen of NOD/SCID mice.
K. Beider, A. Nagler, O. Wald, S. Franitza, M. Dagan-Berger, H. Wald, H. Giladi, S. Brocke, J. Hanna, O. Mandelboim, et al. (2003)
Blood 102, 1951-1958
   Abstract »    Full Text »    PDF »
Macrophages Control the Retention and Trafficking of B Lymphocytes in the Splenic Marginal Zone.
M. C.I. Karlsson, R. Guinamard, S. Bolland, M. Sankala, R. M. Steinman, and J. V. Ravetch (2003)
J. Exp. Med. 198, 333-340
   Abstract »    Full Text »    PDF »
SH2-containing inositol phosphatase (SHIP-1) transiently translocates to raft domains and modulates CD16-mediated cytotoxicity in human NK cells.
R. Galandrini, I. Tassi, G. Mattia, L. Lenti, M. Piccoli, L. Frati, and A. Santoni (2002)
Blood 100, 4581-4589
   Abstract »    Full Text »    PDF »
IMMUNOLOGY: A Perfect Mismatch.
K. Karre (2002)
Science 295, 2029-2031
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882