IL-33, an endogenous danger signal from the IL-1 family
                                Jean-Philippe GIRARD, PhD
        ...
Discovery of NF-HEV, a nuclear factor from high
endothelial venules (Baekkevold …and Girard, Am J Path, 2003, 163:69-79)
 ...
NF-HEV is identical to interleukin-33 (IL-33), an IL-1-
       like cytokine that signals via ST2/IL-1R4
        (Schmitz…...
IL-33 activates various immune cell types




                        (from D. Smith, Clinical & Experimental Allergy, 200...
IL-33 has been linked to important human diseases




 Allergic diseases such as asthma, atopic dermatitis and
 allergic r...
IL-33 is a chromatin-associated IL-1-like cytokine
                         (Carriere, …and Girard, PNAS, 2007, 104:282-28...
Molecular mimicry between IL-33 and Kaposi’s sarcoma
     herpesvirus LANA for attachment to chromatin
                   ...
IL-33 is constitutively expressed in the nucleus
       of endothelial cells from normal human tissues
                 (M...
ATTENTION!
The entire presentation is available to registered
                attendees only!

  To view the rest of this ...
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IL-33, an Endogenous Danger Signal from the IL-1 Family Jean-Philippe Girard, Director, Institute of Pharmacology and Structural Biology, CNRS-University of Toulouse, France

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8th Annual Cytokines and Inflammation Conference, Jan. 28-29, 2010, San Diego, CA

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IL-33, an Endogenous Danger Signal from the IL-1 Family Jean-Philippe Girard, Director, Institute of Pharmacology and Structural Biology, CNRS-University of Toulouse, France

  1. 1. IL-33, an endogenous danger signal from the IL-1 family Jean-Philippe GIRARD, PhD Director, Institute of Pharmacology and Structural Biology (IPBS-CNRS, a 260-people Institute from CNRS and Université de Toulouse) Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
  2. 2. Discovery of NF-HEV, a nuclear factor from high endothelial venules (Baekkevold …and Girard, Am J Path, 2003, 163:69-79) High endothelial venules (HEV): specialized blood vessels for lymphocyte migration (Girard and Springer, Immunol. Today, 1995; Girard and Springer, Immunity, 1995; Lacorre ...and Girard, Blood, 2004) HUMAN TONSIL HEV A MECA-79 DAPI MECA-79 lumen lumen B NF-HEV DAPI NF-HEV SULFATED EPITOPE MECA-79 lumen lumen Blood C MERGE DAPI MERGE Lymphocytes, dendritic cells, .. lumen lumen Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
  3. 3. NF-HEV is identical to interleukin-33 (IL-33), an IL-1- like cytokine that signals via ST2/IL-1R4 (Schmitz…and Kastelein, Immunity, 2005; Chackerian et al., J Immunol 2007) NF-HEV/IL-33 (30.7 kDa) IL-33 IL-1 IL-1a IL-1RAcP IL-1RAcP (30.6 kDa) ST2 IL-1R IL-1b (30.7 kDa) IL-33 Th2 cell MyD88 MyD88 Mast cell IRAK IRAK TRAF6 TRAF6 ST2 mRNA NF-kB MAP kinases IL-4 IL-5 IL-13 Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
  4. 4. IL-33 activates various immune cell types (from D. Smith, Clinical & Experimental Allergy, 2009, 1-9) Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
  5. 5. IL-33 has been linked to important human diseases Allergic diseases such as asthma, atopic dermatitis and allergic rhinitis (Schmitz et al. Immunity 2005; Gudbjartsson et al., Nat Genet 2009; Pushparaj et al., PNAS 2009; …) IL-33 IL-1RAcP Rheumatoid arthritis (Carriere et al. PNAS 2007; Xu et al., ST2 PNAS 2008; Palmer et al., Arthritis Rheum 2009; …) Cardiovascular diseases (atherosclerosis, myocardial MyD88 infarction, heart failure; Sanada et al., J Clin Invest 2007; IRAK Miller et al., J Exp Med 2008; …) TRAF6 Alzheimer’s disease (Chapuis et al., Mol Psychiatry 2009) Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
  6. 6. IL-33 is a chromatin-associated IL-1-like cytokine (Carriere, …and Girard, PNAS, 2007, 104:282-287) IL-33 HEV NF-HEV / IL-33 DAPI IL-33 Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
  7. 7. Molecular mimicry between IL-33 and Kaposi’s sarcoma herpesvirus LANA for attachment to chromatin (Roussel …and Girard, EMBO Reports, 2008, 9:1006-1012) KSHV episome LANA CB M CB M Barbera …and Kaye, Science 2006 Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
  8. 8. IL-33 is constitutively expressed in the nucleus of endothelial cells from normal human tissues (Moussion*, Ortega* and Girard, PLoS ONE, 2008, 3(10):e3331) Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
  9. 9. ATTENTION! The entire presentation is available to registered attendees only! To view the rest of this exciting presentation and many more! Please Register for the 8th Annual Cytokines & Inflammation Conference at www.gtcbio.com If you are already registered, please contact GTCbio for the full version.
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