Klaus Okkenhaug

Summary

Affiliation: Institute for Animal Health
Country: UK

Publications

  1. ncbi request reprint Cutting edge: the phosphoinositide 3-kinase p110 delta is critical for the function of CD4+CD25+Foxp3+ regulatory T cells
    Daniel T Patton
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 177:6598-602. 2006
  2. ncbi request reprint The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells
    Klaus Okkenhaug
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 177:5122-8. 2006
  3. doi request reprint PI3Ks in lymphocyte signaling and development
    Klaus Okkenhaug
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK
    Curr Top Microbiol Immunol 346:57-85. 2010
  4. pmc Antigen receptor signalling: a distinctive role for the p110delta isoform of PI3K
    Klaus Okkenhaug
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, UK, CB2 4AT
    Trends Immunol 28:80-7. 2007
  5. ncbi request reprint Phosphoinositide 3-kinase in T cell activation and survival
    K Okkenhaug
    Laboratory of Lymphocyte Signalling and Development, Molecular Immunology Programme, Babraham Institute, Cambridge CB2 4AT, U K
    Biochem Soc Trans 32:332-5. 2004
  6. ncbi request reprint PI3K in lymphocyte development, differentiation and activation
    Klaus Okkenhaug
    Molecular Immunology Programme, The Babraham Institute, Cambridge CB2 4AT, UK
    Nat Rev Immunol 3:317-30. 2003
  7. pmc Pten loss in CD4 T cells enhances their helper function but does not lead to autoimmunity or lymphoma
    Dalya R Soond
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, United Kingdom
    J Immunol 188:5935-43. 2012
  8. ncbi request reprint CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer
    Fabien Garcon
    Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
    Blood 111:1464-71. 2008
  9. pmc The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development
    Faruk Ramadani
    1Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, UK
    Sci Signal 3:ra60. 2010
  10. doi request reprint PI3Kβ plays a critical role in neutrophil activation by immune complexes
    Suhasini Kulkarni
    Inositide Laboratory, The Babraham Institute, Cambridge CB22 3AT, UK
    Sci Signal 4:ra23. 2011

Collaborators

Detail Information

Publications42

  1. ncbi request reprint Cutting edge: the phosphoinositide 3-kinase p110 delta is critical for the function of CD4+CD25+Foxp3+ regulatory T cells
    Daniel T Patton
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 177:6598-602. 2006
    ..The identification of p110delta as an intracellular signaling protein that regulates the activity of CD4+CD25+Foxp3+ Tregs may facilitate the further elucidation of the molecular mechanisms responsible for Treg-mediated suppression...
  2. ncbi request reprint The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells
    Klaus Okkenhaug
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 177:5122-8. 2006
    ..Thus, p110delta contributes significantly to Th cell expansion and differentiation in vitro and in vivo, also in the context of CD28 costimulation...
  3. doi request reprint PI3Ks in lymphocyte signaling and development
    Klaus Okkenhaug
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK
    Curr Top Microbiol Immunol 346:57-85. 2010
    ..Each of these classes of receptors activates phosphoinositide 3-kinase (PI3K). In this chapter, we summarize current understanding of how PI3K contributes to key aspects of the adaptive immune system...
  4. pmc Antigen receptor signalling: a distinctive role for the p110delta isoform of PI3K
    Klaus Okkenhaug
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, UK, CB2 4AT
    Trends Immunol 28:80-7. 2007
    ..The p110delta isoform of PI3K is the main source of PI3K activity following antigen recognition by B cells, T cells and mast cells. Here, we review the roles of p110delta in regulating antigen-dependent responses in these cell types...
  5. ncbi request reprint Phosphoinositide 3-kinase in T cell activation and survival
    K Okkenhaug
    Laboratory of Lymphocyte Signalling and Development, Molecular Immunology Programme, Babraham Institute, Cambridge CB2 4AT, U K
    Biochem Soc Trans 32:332-5. 2004
    ..Thus a model emerges whereby PI3K is involved in both TcR and CD28 signalling, but each receptor may only exploit a subset of the signalling pathways potentially controlled by PI3K activation...
  6. ncbi request reprint PI3K in lymphocyte development, differentiation and activation
    Klaus Okkenhaug
    Molecular Immunology Programme, The Babraham Institute, Cambridge CB2 4AT, UK
    Nat Rev Immunol 3:317-30. 2003
    ..Additional recent work has provided new insights into the molecular interactions that lead to PI3K activation and the signalling pathways that are regulated by PI3K...
  7. pmc Pten loss in CD4 T cells enhances their helper function but does not lead to autoimmunity or lymphoma
    Dalya R Soond
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, United Kingdom
    J Immunol 188:5935-43. 2012
    ..However, in contrast with models of thymocyte-specific Pten deletion, lymphomas and autoimmunity were not observed, even in older OX40(Cre)Pten(f) mice. Hence loss of Pten enhances Th cell function without obvious deleterious effects...
  8. ncbi request reprint CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer
    Fabien Garcon
    Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
    Blood 111:1464-71. 2008
    ..Consistent with this, CD28 and p110delta double-deficient mice were severely immune compromised. We therefore suggest that combined pharmaceutic targeting of p110delta activity and CD28 costimulation has potent therapeutic potential...
  9. pmc The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development
    Faruk Ramadani
    1Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, UK
    Sci Signal 3:ra60. 2010
    ..These studies indicate that either p110alpha or p110delta can mediate tonic signaling from the BCR, but only p110delta can contribute to antigen-dependent activation of B cells...
  10. doi request reprint PI3Kβ plays a critical role in neutrophil activation by immune complexes
    Suhasini Kulkarni
    Inositide Laboratory, The Babraham Institute, Cambridge CB22 3AT, UK
    Sci Signal 4:ra23. 2011
    ..These results define PI3Kβ as a potential therapeutic target in inflammatory disease...
  11. pmc The PI3K p110δ regulates expression of CD38 on regulatory T cells
    Daniel T Patton
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    PLoS ONE 6:e17359. 2011
    ..Therefore, CD38 can be used as a marker for Tregs with high suppressive activity and the impaired Treg function in p110δ(D910A) mice can in part be explained by the failure of CD38(high) cells to develop...
  12. doi request reprint Cutting edge: the Foxp3 target miR-155 contributes to the development of regulatory T cells
    Susan Kohlhaas
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 182:2578-82. 2009
    ..However, we found no evidence for defective suppressor activity of miR-155-deficient Tregs, either in vitro or in vivo. Our results indicate that miR-155 contributes to Treg development, but that additional miRNAs control Treg function...
  13. pmc p110gamma and p110delta isoforms of phosphoinositide 3-kinase differentially regulate natural killer cell migration in health and disease
    Aurore Saudemont
    Laboratory of Lymphocyte Signalling, The Babraham Institute, CB22 3AT Cambridge, United Kingdom
    Proc Natl Acad Sci U S A 106:5795-800. 2009
    ..These results implicate p110delta downstream of GPCRs in NK cells and highlight its nonredundant role as a key regulator of NK cell trafficking in health and disease...
  14. doi request reprint Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction
    Julia Rolf
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 185:4042-52. 2010
    ..Our findings support a model in which the magnitude of the GC reaction is controlled by the activity of the PI3K pathway in T(FH) cells...
  15. pmc PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans
    Dalya R Soond
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    Blood 115:2203-13. 2010
    ..There is therefore a strong rationale for p110delta inhibitors to be considered for therapeutic use in T-cell-mediated autoimmune and inflammatory diseases...
  16. doi request reprint Rules of engagement: distinct functions for the four class I PI3K catalytic isoforms in immunity
    Klaus Okkenhaug
    Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, United Kingdom
    Ann N Y Acad Sci 1280:24-6. 2013
    ....
  17. ncbi request reprint P-Rex1 regulates neutrophil function
    Heidi C E Welch
    Inositide Laboratory, The Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, United Kingdom
    Curr Biol 15:1867-73. 2005
    ..In conclusion, P-Rex1 is an important regulator of neutrophil function by mediating a subset of Rac-dependent neutrophil responses. However, P-Rex1 is not an essential regulator of neutrophil chemotaxis and degranulation...
  18. doi request reprint Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage
    Ivan Angulo
    Department of Medicine, University of Cambridge, Cambridge, UK
    Science 342:866-71. 2013
    ..Selective p110δ inhibitors IC87114 and GS-1101 reduced the activity of the mutant enzyme in vitro, which suggested a therapeutic approach for patients with APDS. ..
  19. pmc Does the PI3K pathway promote or antagonize regulatory T cell development and function?
    Dalya R Soond
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute Cambridge, UK
    Front Immunol 3:244. 2012
    ....
  20. ncbi request reprint Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils
    Alison M Condliffe
    The Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, UK
    Blood 106:1432-40. 2005
    ..These results start to define which PI3K isoforms are responsible for modulating neutrophil responsiveness to infection and inflammation...
  21. doi request reprint Signaling by the phosphoinositide 3-kinase family in immune cells
    Klaus Okkenhaug
    Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, CB22 3AT, United Kingdom
    Annu Rev Immunol 31:675-704. 2013
    ..Our understanding of the PI3Ks in immunity is guided by fundamental discoveries made in simpler model organisms as well as by appreciating new adaptations of this signaling module in mammals in general and in immune cells in particular...
  22. ncbi request reprint The PI3K p110delta controls T-cell development, differentiation and regulation
    D T Patton
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK
    Biochem Soc Trans 35:167-71. 2007
    ..Moreover, p110delta is critical for Treg (regulatory T-cell) function. Here, we review the role of PI3Ks in T-cell development and function...
  23. ncbi request reprint p110delta is required for innate immunity to transplantable lymphomas
    A Saudemont
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge, UK
    Biochem Soc Trans 35:183-5. 2007
    ..Our results show for the first time a critical role for p110delta in NK cell biology in vivo...
  24. ncbi request reprint Cutting edge: differential roles for phosphoinositide 3-kinases, p110gamma and p110delta, in lymphocyte chemotaxis and homing
    Karin Reif
    Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA
    J Immunol 173:2236-40. 2004
    ..These observations establish that p110gamma and p110delta function in lymphocyte chemotaxis, and show differential roles for PI3K family members in B and T cell migration...
  25. doi request reprint Proliferative signals mediated by CD28 superagonists require the exchange factor Vav1 but not phosphoinositide 3-kinase in primary peripheral T cells
    Tea Gogishvili
    Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, Germany
    Eur J Immunol 38:2528-33. 2008
    ..Although we did not address the role of Grb2 in CD28 signalling, these results indicate that CD28 can mediate Lck- and Vav1-dependent proliferative signals independently of PI3K...
  26. pmc Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking
    Linda V Sinclair
    Department of Cell Biology and Immunology, University of Dundee, Dundee DD1 5EH, UK
    Nat Immunol 9:513-21. 2008
    ..PI(3)K-mTOR nutrient-sensing pathways also determined expression of the chemokine receptor CCR7 and regulated lymphocyte trafficking in vivo. Hence, lymphocytes use PI(3)K and mTOR to match metabolism and trafficking...
  27. pmc T cell receptor-induced phosphoinositide-3-kinase p110delta activity is required for T cell localization to antigenic tissue in mice
    Sarah J Jarmin
    Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom
    J Clin Invest 118:1154-64. 2008
    ..These observations suggest that pharmacological targeting of p110delta activity is a viable strategy for the therapy of T cell-mediated pathology...
  28. ncbi request reprint Gene-targeting reveals physiological roles and complex regulation of the phosphoinositide 3-kinases
    Lazaros C Foukas
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
    Arch Biochem Biophys 414:13-8. 2003
    ..In addition, these experiments have brought the complexity of how PI3K activation is regulated into focus...
  29. ncbi request reprint Essential role for the p110delta phosphoinositide 3-kinase in the allergic response
    Khaled Ali
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
    Nature 431:1007-11. 2004
    ..Inactivation of p110delta protects mice against anaphylactic allergic responses. These results identify p110delta as a new target for therapeutic intervention in allergy and mast-cell-related pathologies...
  30. ncbi request reprint CD28 regulates the translation of Bcl-xL via the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway
    Linda X Wu
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
    J Immunol 174:180-94. 2005
    ..These results demonstrate that CD28 relieves the translational inhibition of Bcl-x(L) in a PI3K/mammalian target of rapamycin-dependent manner...
  31. ncbi request reprint Key role of the p110delta isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110delta function in B cells
    Antonio Bilancio
    Ludwig Institute for Cancer Research, 91 Riding House Street, London, W1W 7BS, United Kingdom
    Blood 107:642-50. 2006
    ....
  32. ncbi request reprint Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation
    Lazaros C Foukas
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
    Nature 441:366-70. 2006
    ..These findings demonstrate a critical role for p110alpha in growth factor and metabolic signalling and also suggest an explanation for selective mutation or overexpression of p110alpha in a variety of cancers...
  33. ncbi request reprint Physiologic and aberrant regulation of memory T-cell trafficking by the costimulatory molecule CD28
    Vincenzo Mirenda
    Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom
    Blood 109:2968-77. 2007
    ..These findings highlight a novel physiologic function of CD28 that has crucial implications for the therapeutic manipulation of this and other costimulatory molecules...
  34. ncbi request reprint Role of the phosphoinositide 3-kinase p110delta in generation of type 2 cytokine responses and allergic airway inflammation
    Baher F Nashed
    CIHR National Training Program in Allergy and Asthma Research and Department of Immunology, University of Manitoba, Winnipeg, Canada
    Eur J Immunol 37:416-24. 2007
    ..These data demonstrate a novel functional role for p110delta signaling in induction of type 2 responses in vivo and may offer a new therapeutic target for Th2-mediated airway disease...
  35. ncbi request reprint Requirement for phosphoinositide 3-kinase p110delta signaling in B cell antigen receptor-mediated antigen presentation
    Monther M Al-Alwan
    Department of Immunology, University of Manitoba, Winnipeg, Canada
    J Immunol 178:2328-35. 2007
    ..Our data demonstrate a role for p110delta signaling in B cell Ag presentation function, implicating 3-phosphoinositides and their targets in the latter stages of this process...
  36. pmc Requirement of bic/microRNA-155 for normal immune function
    Antony Rodriguez
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    Science 316:608-11. 2007
    ..Our work suggests that bic/microRNA-155 plays a key role in the homeostasis and function of the immune system...
  37. ncbi request reprint A two-signal model for T cell trafficking
    Federica M Marelli-Berg
    Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK, W12 0NN
    Trends Immunol 28:267-73. 2007
    ..The implications for therapeutic strategies manipulating these signals are discussed...
  38. ncbi request reprint Inactivation of PI3Kgamma and PI3Kdelta distorts T-cell development and causes multiple organ inflammation
    Hong Ji
    Merck Serono S A, Geneva Research Center, Geneva, Switzerland
    Blood 110:2940-7. 2007
    ..Thus, the pathology in the p110gammadelta-deficient mice is likely to be secondary to a developmental block in the thymus that leads to lymphopenia-associated inflammatory responses...
  39. ncbi request reprint Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice
    Klaus Okkenhaug
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
    Science 297:1031-4. 2002
    ..They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity...
  40. pmc Role of the p110delta PI 3-kinase in integrin and ITAM receptor signalling in platelets
    Yotis A Senis
    Centre for Cardiovascular Sciences, Division of Medical Sciences, Institute of Biomedical Research, Wolfson Drive, The Medical School, University of Birmingham, Edgbaston, Birmingham, UK
    Platelets 16:191-202. 2005
    ..The more pronounced inhibitory effect of LY294002 and wortmannin indicates that other isoforms of PI 3-kinase play a more significant role in signalling by the two platelet glycoprotein receptors...
  41. ncbi request reprint Class I phosphoinositide 3-kinase p110beta is required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by macrophages
    Yann Leverrier
    Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, 91 Riding House Street, London W1W 7BS, United Kingdom
    J Biol Chem 278:38437-42. 2003
    ..Our findings demonstrate that p110beta is the major class I catalytic isoform required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by primary macrophages...
  42. pmc The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma
    Julie Guillermet-Guibert
    Center for Cell Signaling, Institute of Cancer, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom
    Proc Natl Acad Sci U S A 105:8292-7. 2008
    ..p110beta, which shows a much broader tissue distribution than the leukocyte-restricted p110gamma, could thus provide a conduit for GPCR-linked PI3K signaling in the many cell types where p110gamma expression is low or absent...