Robert A Kastelein

Summary

Affiliation: Schering-Plough Research Institute
Country: USA

Publications

  1. pmc Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract
    Alexander M Owyang
    Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Exp Med 203:843-9. 2006
  2. pmc Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis
    Yi Chen
    Discovery Research, Schering Plough Biopharma, Palo Alto, California 94304, USA
    J Clin Invest 116:1317-26. 2006
  3. ncbi request reprint IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells
    Stefan Pflanz
    DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA
    Immunity 16:779-90. 2002
  4. ncbi request reprint IL-12 and IL-23: master regulators of innate and adaptive immunity
    Claire L Langrish
    Discovery Research, DNAX Research Inc, Palo Alto, CA 94304, USA
    Immunol Rev 202:96-105. 2004
  5. pmc IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis
    Jason R Chan
    Discovery Research, Schering Plough Biopharma Formerly DNAX Research, Inc, Palo Alto, CA 94304, USA
    J Exp Med 203:2577-87. 2006
  6. ncbi request reprint Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation
    Robert A Kastelein
    Discovery Research, Schering Plough Biopharma, Palo Alto, California 94304 1104, USA
    Annu Rev Immunol 25:221-42. 2007
  7. doi request reprint IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells
    Caroline Diveu
    Department of Immunology, Schering Plough Biopharma, Palo Alto, CA 94304, USA
    J Immunol 182:5748-56. 2009
  8. pmc IL-25 regulates Th17 function in autoimmune inflammation
    Melanie A Kleinschek
    Discovery Research, Schering Plough Biopharma, Palo Alto, CA 94304, USA
    J Exp Med 204:161-70. 2007
  9. ncbi request reprint WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27
    Stefan Pflanz
    DNAX Research Institute, Palo Alto, CA 94304, USA
    J Immunol 172:2225-31. 2004
  10. ncbi request reprint IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex
    Alissa A Chackerian
    Discovery Research, Schering Plough Biopharma Formerly DNAX Research, Palo Alto, CA 94304, USA
    J Immunol 179:2551-5. 2007

Collaborators

Detail Information

Publications43

  1. pmc Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract
    Alexander M Owyang
    Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Exp Med 203:843-9. 2006
    ..Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract...
  2. pmc Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis
    Yi Chen
    Discovery Research, Schering Plough Biopharma, Palo Alto, California 94304, USA
    J Clin Invest 116:1317-26. 2006
    ..Thus, therapeutic targeting of IL-23 effectively inhibited multiple inflammatory pathways that are critical for driving CNS autoimmune inflammation...
  3. ncbi request reprint IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells
    Stefan Pflanz
    DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA
    Immunity 16:779-90. 2002
    ..It also strongly synergizes with IL-12 to trigger IFN-gamma production of naive CD4(+) T cells. IL-27 mediates its biologic effects through the orphan cytokine receptor WSX-1/TCCR...
  4. ncbi request reprint IL-12 and IL-23: master regulators of innate and adaptive immunity
    Claire L Langrish
    Discovery Research, DNAX Research Inc, Palo Alto, CA 94304, USA
    Immunol Rev 202:96-105. 2004
    ..These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression...
  5. pmc IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis
    Jason R Chan
    Discovery Research, Schering Plough Biopharma Formerly DNAX Research, Inc, Palo Alto, CA 94304, USA
    J Exp Med 203:2577-87. 2006
    ..IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target...
  6. ncbi request reprint Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation
    Robert A Kastelein
    Discovery Research, Schering Plough Biopharma, Palo Alto, California 94304 1104, USA
    Annu Rev Immunol 25:221-42. 2007
    ..In this review, we aim to highlight the discoveries that have led to our current understanding of the biology of IL-23 and IL-27 in the context of their role in resistance to infection, immune-mediated inflammation, and cancer...
  7. doi request reprint IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells
    Caroline Diveu
    Department of Immunology, Schering Plough Biopharma, Palo Alto, CA 94304, USA
    J Immunol 182:5748-56. 2009
    ..These results show that IL-27 acts as a negative regulator of the developing IL-17A response in vivo, suggesting a potential therapeutic role for IL-27 in autoimmune diseases...
  8. pmc IL-25 regulates Th17 function in autoimmune inflammation
    Melanie A Kleinschek
    Discovery Research, Schering Plough Biopharma, Palo Alto, CA 94304, USA
    J Exp Med 204:161-70. 2007
    ..Thus, IL-25 and IL-17, being members of the same cytokine family, play opposing roles in the pathogenesis of organ-specific autoimmunity...
  9. ncbi request reprint WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27
    Stefan Pflanz
    DNAX Research Institute, Palo Alto, CA 94304, USA
    J Immunol 172:2225-31. 2004
    ..Thus, IL-27 not only contributes to the development of an adaptive immune response through its action on CD4(+) T cells, it also directly acts on cells of the innate immune system...
  10. ncbi request reprint IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex
    Alissa A Chackerian
    Discovery Research, Schering Plough Biopharma Formerly DNAX Research, Palo Alto, CA 94304, USA
    J Immunol 179:2551-5. 2007
    ..The implications of this shared usage of IL-1RAcP by IL-1(alpha and beta) and IL-33 are discussed...
  11. pmc IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
    Claire L Langrish
    Discovery Research, DNAX Research Inc, Palo Alto, CA 94304, USA
    J Exp Med 201:233-40. 2005
    ..Using passive transfer studies, we confirm that these IL-23-dependent CD4(+) T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity...
  12. pmc Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling
    Katia Boniface
    Department of Immunology, Schering Plough Biopharma, Palo Alto, CA 94304, USA
    J Exp Med 206:535-48. 2009
    ..These findings, together with the altered IL-12/IL-23 balance induced by PGE2 in dendritic cells, further highlight the crucial role of the inflammatory microenvironment in Th17 cell development and regulation...
  13. pmc IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6
    David Yen
    Department of Discovery Research, Schering Plough Biopharma, Palo Alto, California 94304, USA
    J Clin Invest 116:1310-6. 2006
    ..This pathway may be responsible for chronic intestinal inflammation as well as other chronic autoimmune inflammatory diseases...
  14. ncbi request reprint IL-23 promotes tumour incidence and growth
    John L Langowski
    Schering Plough Biopharma, 901 California Avenue, Palo Alto, California 94304, USA
    Nature 442:461-5. 2006
    ..We show that IL-23 is an important molecular link between tumour-promoting pro-inflammatory processes and the failure of the adaptive immune surveillance to infiltrate tumours...
  15. ncbi request reprint Development, cytokine profile and function of human interleukin 17-producing helper T cells
    Nicholas J Wilson
    Department of Discovery Research, Schering Plough Biopharma Formerly DNAX Research, Palo Alto, California 94304 1104, USA
    Nat Immunol 8:950-7. 2007
    ..Our data collectively indicate that human and mouse T(H)-17 cells require distinct factors during differentiation and that human T(H)-17 cells may regulate innate immunity in epithelial cells...
  16. doi request reprint IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4-CD8- entheseal resident T cells
    Jonathan P Sherlock
    Merck Research Laboratories, Palo Alto, California, USA
    Nat Med 18:1069-76. 2012
    ....
  17. pmc Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation
    Craig A Murphy
    Discovery Research, DNAX Research Inc, Palo Alto, CA 94304, USA
    J Exp Med 198:1951-7. 2003
    ..The data presented here indicate that IL-23 is an essential promoter of end-stage joint autoimmune inflammation, whereas IL-12 paradoxically mediates protection from autoimmune inflammation...
  18. pmc Neutralization or absence of the interleukin-23 pathway does not compromise immunity to mycobacterial infection
    Alissa A Chackerian
    Discovery Research and Experimental Pathology and Pharmacology, Schering Plough Biopharma, 901 California Ave, Palo Alto, CA 94304 1104, USA
    Infect Immun 74:6092-9. 2006
    ..Furthermore, neutralization of IL-23 or IL-17A does not increase susceptibility to mycobacterial BCG infection...
  19. ncbi request reprint IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines
    Jochen Schmitz
    Schering Plough Biopharma Formerly DNAX Research, Inc, 901 California Avenue, Palo Alto, California 94304, USA
    Immunity 23:479-90. 2005
    ..In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs...
  20. ncbi request reprint Swords into plowshares: IL-23 repurposes tumor immune surveillance
    John L Langowski
    Schering Plough Biopharma, 901 California Avenue, Palo Alto, CA 94304, USA
    Trends Immunol 28:207-12. 2007
    ..Consequently, IL-23 enables the persistence of the recognized tumor cells, accompanied by tumor-associated inflammation. This concept can explain tumor growth in the presence of large quantities of tumor-specific T cells...
  21. pmc Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation
    Melanie A Kleinschek
    Department of Immunology, Schering Plough Biopharma, Palo Alto, CA 94304, USA
    J Exp Med 206:525-34. 2009
    ..Our data identify CD161(+) CD4 T cells as a resting Th17 pool that can be activated by IL-23 and mediate destructive tissue inflammation...
  22. ncbi request reprint Understanding the IL-23-IL-17 immune pathway
    Brent S McKenzie
    Discovery Research, DNAX Research Inc, 901 California Ave, Palo Alto, CA 94304 1104, USA
    Trends Immunol 27:17-23. 2006
    ..By comparing the pathophysiological function of IL-12 and IL-23 in the context of host defense and autoimmune inflammation, we are beginning to understand the novel IL-23-IL-17 immune pathway...
  23. ncbi request reprint Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain
    Daniel J Cua
    Department of Immunology, DNAX Research Inc, Palo Alto, California 94304 1104, USA
    Nature 421:744-8. 2003
    ..In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages...
  24. pmc Biomarkers of Therapeutic Response in the IL-23 Pathway in Inflammatory Bowel Disease
    Corinne Cayatte
    Merck Research Laboratories formerly Schering Plough Biopharma, Palo Alto, California, USA
    Clin Transl Gastroenterol 3:e10. 2012
    ..As biomarkers of disease state and treatment efficacy are becoming increasingly important in drug development, we sought to identify efficacy biomarkers for anti-IL-23 therapy in Crohn's disease (CD)...
  25. ncbi request reprint The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses
    Giorgio Trinchieri
    Schering Plough Research Institute, Laboratory for Immunological Research, 69571 Dardilly, France
    Immunity 19:641-4. 2003
    ..2003; Villarino et al., 2003), indicate that they mediate complex and well-differentiated functions...
  26. ncbi request reprint IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells
    Linda Hibbert
    Department of Discovery Biology, DNAX Research Institute, Palo Alto, CA 94304, USA
    J Interferon Cytokine Res 23:513-22. 2003
    ..We propose that IL-27 and IFN-alpha are important for early Th1 commitment and act upstream of IL-12 and IFN-gamma in this pathway...
  27. ncbi request reprint A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R
    Christi Parham
    Department of Immunology, DNAX Research, Palo Alto, CA 94304, USA
    J Immunol 168:5699-708. 2002
    ..The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rbeta2...
  28. ncbi request reprint Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP
    Vassili Soumelis
    DNAX, 901 California Avenue, Palo Alto, CA 94304, USA
    Nat Immunol 3:673-80. 2002
    ..TSLP expression was associated with Langerhans cell migration and activation in situ. These findings shed new light on the function of human TSLP and the role played by epithelial cells and DCs in initiating allergic inflammation...
  29. ncbi request reprint IL-23 production by cosecretion of endogenous p19 and transgenic p40 in keratin 14/p40 transgenic mice: evidence for enhanced cutaneous immunity
    Tamara Kopp
    Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, Vienna International Research Cooperation Center, Vienna, Austria
    J Immunol 170:5438-44. 2003
    ..7 days, p < 0.01). Based on these results we propose that IL-23-induced changes of LC may be an important mechanism in directing the outcome of cutaneous immune responses...
  30. ncbi request reprint TGF-beta, a 'double agent' in the immune pathology war
    Daniel J Cua
    Nat Immunol 7:557-9. 2006
  31. ncbi request reprint IL-27 limits IL-2 production during Th1 differentiation
    Alejandro V Villarino
    Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA
    J Immunol 176:237-47. 2006
    ....
  32. ncbi request reprint Novel IL-12 family members shed light on the orchestration of Th1 responses
    Frank Brombacher
    University of Cape Town, Division of Immunology, Groote Schuur Hospital, 7925 Cape Town, South Africa
    Trends Immunol 24:207-12. 2003
    ..Finally, IL-27, the latest addition to this family, is a heterodimer composed of the p40-related protein EBI3 (Epstein-Barr virus-induced gene 3) and the p35-related protein p28. IL-27 is involved in early Th1 initiation...
  33. ncbi request reprint The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection
    Alejandro Villarino
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St, Philadelphia, PA 19104, USA
    Immunity 19:645-55. 2003
    ....
  34. ncbi request reprint IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12
    Linda A Lieberman
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Immunol 173:1887-93. 2004
    ..Together, these studies indicate that IL-12, not IL-23, plays a dominant role in resistance to toxoplasmosis but, in the absence of IL-12, IL-23 can provide a limited mechanism of resistance to this infection...
  35. ncbi request reprint IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12
    Melanie A Kleinschek
    Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany
    J Immunol 176:1098-106. 2006
    ..These results show that IL-23 complements the more dominant role of IL-12 in protection against a chronic fungal infection by an enhanced inflammatory cell response and distinct cytokine regulation...
  36. ncbi request reprint Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis
    Ivo Sonderegger
    Institute of Integrative Biology, Molecular Biomedicine, ETH Zurich, Switzerland
    Eur J Immunol 36:2849-56. 2006
    ..Thus, targeting of IL-23 and IL-17 by passive and active vaccination strategies holds promise as a therapeutic approach to treat patients at risk for development of dilated cardiomyopathy...
  37. pmc Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine
    Colby Zaph
    Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Exp Med 205:2191-8. 2008
    ..We propose that acquisition of, or alterations in, commensal bacteria influences intestinal immune homeostasis via direct regulation of the IL-25-IL-23-IL-17 axis...
  38. pmc Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells
    Franca Gerosa
    Department of Pathology, Section of Immunology, University of Verona, 37134 Verona, Italy
    J Exp Med 205:1447-61. 2008
    ..Thus, the differential ability of pathogens to induce antigen-presenting cells to produce cytokines regulates the immune response to infection...
  39. ncbi request reprint IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance
    Teresa Zelante
    Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    Eur J Immunol 37:2695-706. 2007
    ..As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi...
  40. pmc Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant
    Willem W Overwijk
    Division of Immunology, The Netherlands Cancer Institute, 1105 AZ Amsterdam, The Netherlands
    J Immunol 176:5213-22. 2006
    ..Collectively, these results suggest that IL-23 is a potent vaccine adjuvant for the induction of therapeutic, tumor-specific CD8(+) T cell responses...
  41. ncbi request reprint Differential effects of IL-27 on human B cell subsets
    Frederique Larousserie
    Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8147, Universite Paris V, Institut Fédératif de Recherche Necker, 161 rue de Sevres, 75 015 Paris, France
    J Immunol 176:5890-7. 2006
    ..These data indicate that the B cell response to IL-27 is modulated during B cell differentiation and varies depending on the mode of B cell activation...
  42. ncbi request reprint Borrelia burgdorferi potently activates bone marrow-derived conventional dendritic cells for production of IL-23 required for IL-17 release by T cells
    Jens Knauer
    Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany
    FEMS Immunol Med Microbiol 49:353-63. 2007
    ..These in vitro data describing a spirochete-induced release of IL-23 may help to define IL-17-dependent inflammatory responses in the disease...
  43. ncbi request reprint Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice
    Charles O Elson
    Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294 0007, USA
    Gastroenterology 132:2359-70. 2007
    ..Interleukin (IL)-23 supports a distinct lineage of T cells producing IL-17 (Th17) that can mediate chronic inflammation. This study was performed to define the role of IL-23 and Th17 cells in chronic colitis in mice...